Anti-microbial blue light systems and methods

ABSTRACT

Systems, devices and methods for controlled intramedullary delivery of light (frequencies from about 380 nm to about 500 nm) to treat tissue or bones disorders, including osteomyelitis, by a flexible fiber are provided, where the light is delivered in a circumferential fashion around the fiber, and where the energy delivered from the fiber is of a similar average intensity at the front end and back end of the fiber, and in between. The methods and systems deliver intramedullary light to the canal over long lengths via a minimally invasive pathway to a bone. The methods and systems deliver and maintain a light delivery system within the canal of the bone to provide single or multiple doses of light to kill, eliminate, remove or reduce bacteria, viruses, fungus and pathogens, without removal of the light fiber system, thereby providing single or multiple treatments.

RELATED APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalApplication No. 63/264,174 filed Nov. 17, 2021, and U.S. ProvisionalApplication No. 63/238,104 filed Aug. 27, 2021, and the contents of eachof these applications are hereby incorporated herein by reference intheir entireties.

FIELD

The embodiments disclosed herein relate to treatments for bones, andmore particularly to anti-microbial blue light systems and methods forproviding an anti-microbial, anti-bacterial effect for medicalapplications.

BACKGROUND

Bones form the skeleton of the body and allow the body to be supportedagainst gravity and to move and function in the world. Bone fracturescan occur, for example, from an outside force or from a controlledsurgical cut (an osteotomy). A fracture's alignment is described as towhether the fracture fragments are displaced or in their normal anatomicposition. In some instances, surgery may be required to re-align andstabilize the fractured bone. A bone infection may occur when bacteriaor fungi invade the bone, such as when a bone is fractured or from bonefracture repair. These bacteria commonly appear and if not addressedproperly can cause server health problems. It would be desirable to havean improved systems and methods for eliminating bacteria or otherpathogens.

SUMMARY

The present disclosure is directed to systems, devices, and methods forproviding treatment to tissue. In some embodiments, the system caninclude a delivery catheter having an elongated shaft and an inner lumentherethrough and one or more optical fibers sized to pass through theinner lumen of the delivery catheter and being configured to directlydeliver light energy to provide an antimicrobial effect to the tissue.The one or more optical fibers are configured to disperse the lightenergy evenly over a length of the one or more optical fibers in bothlongitudinal and circumferential directions. The antimicrobial effect ofthe light energy is configured to kill bacteria, viruses, or fungus totreat bone infections. The antimicrobial effect of the light energy isconfigured to reduce an amount of one or more pathogens in a bone.

In some embodiments, the one or more optical fibers include a claddingcovering an outer surface thereof, and at least a portion of thecladding of the one or more optical fibers is removed from an outersurface of the one or more optical fibers to achieve the even dispersionof the light energy. In some embodiments, the at least a portion of thecladding is removed to form a helical spiral along the length of the oneor more optical fibers. In some embodiments, the helical spiral becomesincreasingly tight as the helical spiral moves from a proximal end ofthe one or more optical fibers to a distal end of the one or moreoptical fibers to achieve an even light distribution over the length ofthe one or more optical fibers. In some embodiments, a depth of theremoval of the cladding increases as the helical spiral moves from aproximal end of the one or more optical fibers to a distal end of theone or more optical fibers to achieve an even light distribution overthe length of the one or more optical fibers. In some embodiments, thehelical spiral allows for dispersion of light energy around 360 degreesof the one or more optical fibers.

In some embodiment, the one or more optical fibers includes a diffusivemembrane disposed on an outer surface thereof, the diffusive membraneconfigured to be applied to the outer surface of the one or more opticalfibers to achieve the even light distribution over the length of the oneor more optical fibers.

In some embodiments, the light energy has illumination wavelengths fromabout 400 nm to about 475 nm. In some embodiments, the light energy hasillumination wavelengths from about 380 nm to about 500 nm. In someembodiments, the light energy has illumination wavelengths from about405 nm to about 470 nm.

In some embodiments, a system for providing treatment to tissue isprovided and can include a light source configured to provide lightenergy at a plurality of frequencies, a delivery catheter having anelongated shaft and an inner lumen therethrough, and one or more opticalfibers sized to pass through the inner lumen of the delivery catheterand being configured to directly deliver the light energy from the lightsource to provide an antimicrobial effect to the tissue. The one or moreoptical fibers are configured to disperse the light energy evenly over alength of the one or more optical fibers in both longitudinal andcircumferential directions. The antimicrobial effect of the light energyis configured to reduce an amount of, remove, kill or eliminate one ormore pathogens in a bone.

In some embodiments, the plurality of frequencies of the light energyare selected based on the antimicrobial effect on specific microbialtargets for each of the plurality of frequencies of light energy. Insome embodiments, a subset of the plurality of frequencies of lightenergy can be used based on the specific microbial targets. In someembodiments, the light energy has illumination wavelengths from about400 nm to about 475 nm. In some embodiments, the light source is in theform of a chain of a plurality of LEDs such that the chain of theplurality of LEDs can produce even light dispersion over the length ofthe chain.

In some embodiments, the one or more optical fibers include a claddingcovering an outer surface thereof, and wherein at least a portion of thecladding of the one or more optical fibers is removed from an outersurface of the one or more optical fibers to achieve the even dispersionof the light energy. In some embodiments the at least a portion of thecladding is removed to form a helical spiral along the length of the oneor more optical fibers.

In some embodiments, a method for treating tissue is provided and caninclude the steps of delivering a catheter to a tissue, delivering oneor more optical fibers through the catheter to the tissue, activating alight source engaging the one or more optical fibers, and deliveringlight energy from the light source to the one or more optical fibers toprovide an antimicrobial effect to the tissue. The one or more opticalfibers can disperse the light energy evenly over a length of the one ormore optical fibers in both longitudinal and circumferential directions.

In some embodiments the light source includes a plurality of frequenciesof the light energy. In some embodiments, the method can further includeselecting one or more of the plurality of frequencies of light energy toactivate based on the antimicrobial effect on specific microbialtargets. In some embodiments the light energy has illuminationwavelengths from about 400 nm to about 475 nm.

BRIEF DESCRIPTION OF THE DRAWINGS

The presently disclosed embodiments will be further explained withreference to the attached drawings, wherein like structures are referredto by like numerals throughout the several views. The drawings shown arenot necessarily to scale, with emphasis instead generally being placedupon illustrating the principles of the presently disclosed embodiments.

FIG. 1A shows a schematic illustration of an exemplary embodiment of abone implant system;

FIG. 1B and FIG. 1C show exemplary embodiments of a bone implant devicethat includes a delivery catheter and an expandable member sufficientlyshaped to fit within a space, cavity or a gap in a fractured bone;

FIG. 2A shows a close-up cross-sectional view of the region circled inFIG. 1A of the distal end of the delivery catheter and the expandablemember prior to the device being infused with a fluid;

FIG. 2B shows a close-up cross-sectional view of the region circled inFIG. 1A of the distal end of the delivery catheter and the expandablemember after the device has been infused with fluid and light energyfrom the light-conducting fiber is introduced into the deliverycatheter;

FIG. 2C and FIG. 2D each show a close-up cross-sectional view of theregions circled in FIG. 1B and FIG. 1C, respectively, showing the distalend of the delivery catheter and the expandable member and alight-conducting fiber in the delivery catheter and inner lumen of theexpandable member;

FIG. 3A is an exemplary graph of specific spectrum for 5 LEDs;

FIG. 3B is an exemplary graph showing peaks for 5 LEDSs at 405, 415,435, 450 and 475 nm;

FIG. 3C is an exemplary power grid of the spectrum from system havingfive LEDs;

FIG. 3D is an exemplary graph of an adjustment of the power levels ofthree out of five LEDs such that the peak are approaching similarheights;

FIG. 4A, FIG. 4B, FIG. 4C, FIG. 4D and FIG. 4E are exemplary graphsillustrating bacteria reduction over time as it relates to power;

FIG. 5 illustrates exemplary results of the use of five LEDs to treat atissue and/or bone;

FIG. 6A and FIG. 6B show an embodiment of a system with multiple LEDsthat are dialed in via a light box (i.e., switches thrown to pullspecific frequencies), and the ability to drive the various LEDs atdifferent powers (so that the optical output is the same);

FIG. 7A, FIG. 7B, FIG. 7C, and FIG. 7D show exemplary graphs of spectralcurves of the presently disclosed device with various numbers of LEDs;

FIG. 8 , FIG. 9 , and FIG. 10 are exemplary embodiments of an LED with areflecting member;

FIG. 11 is an exemplary embodiment of a plurality of LEDs connectedtogether on a string for delivering light energy to a treatment site;

FIG. 12A shows an exemplary embodiment of a device providing ananti-microbial effect on a bone positioned in a body;

FIG. 12B is an exemplary embodiment of an introduction port forintroducing one or more fibers for providing an anti-microbial effect ona bone;

FIG. 13 illustrates an exemplary graph showing power distribution overthe length of the fiber;

FIG. 14A and FIG. 14B shows that a reflective surface is added to thedistal tip of a light fiber;

FIG. 15A, FIG. 15B, FIG. 15C, and FIG. 15D shows various views of anexemplary embodiment of a fiber with cladding removed in a spiral;

FIG. 16 shows an exemplary embodiment of a fiber with a portion of thecladding removed;

FIG. 17 shows that in some embodiments, the cladding is removed 360degrees around the fiber; and in some embodiments, the cladding is onlyremoved in a 180 degree orientation with the cut side outwards;

FIG. 18 illustrates an exemplary fiber having cladding that changesdepth along the length of the fiber;

FIG. 19 shows that the surface treatment of wounds or the use inconjunction with procedures that require larger area coverage of the ABLlight can be achieved by creating a “wand” from the light fibers;

FIG. 20 illustrates exemplary modes of light source operation that canbe continuous or pulsed;

FIG. 21 shows an exemplary embodiment of a paddle with a plate-shape;

FIG. 22A and FIG. 22B illustrates an exemplary device providing ananti-microbial effect on a bone that can include a series of shorterlength fibers;

FIG. 23A and FIG. 23B illustrates an exemplary fiber positioned relativeto a reflector;

FIG. 24 shows an exemplary embodiment of a device for providing ananti-microbial effect on a bone;

FIG. 25A illustrates an exemplary embodiment of a balloon catheterhaving one or more fibers positioned on the outside thereof;

FIG. 25B illustrates a top view an exemplary embodiment of a ballooncatheter having one or more fibers positioned on the outside thereof;

FIG. 25C illustrates an exemplary fiber with a portion of claddingremoved therefrom;

FIG. 26 shows an exemplary embodiment of a distal end of a ballooncatheter in commutation with expandable member;

FIG. 27 shows an exemplary embodiment of an expandable member havingridges located on an outer surface, wherein the ridges include at leastone channel for the optical fibers to enter there through;

FIG. 28 shows an exemplary channel or channels configured with at leastone or more reflective prisms, i.e. magnification devices, formagnifying light from the optical fibers;

FIG. 29 shows an exemplary ridge or ridges configured to include atleast one or more reflective prisms, i.e. magnification devices;

FIG. 30A shows an exemplary embodiment of a manifold located at aproximal end of the expandable member;

FIG. 30B shows an exemplary embodiment of a manifold located in a lumenat a distal area of the expandable member;

FIG. 31A, FIG. 31B and FIG. 31C show views of a distal end of a devicehaving a removable cap for repairing a weakened or fractured bone of thepresent disclosure, according to embodiments of the disclosure;

FIG. 32 shows an embodiment of an optical fiber of the presentdisclosure fabricated from a flexible light transmitting material thatcan be inserted into at least one channel, according to embodiments ofthe disclosure;

FIG. 33 shows a view of another embodiment of a distal end of a ballooncatheter of the present disclosure, which is similar to FIG. 26 ,wherein the optical fiber has a pre-defined shape specific to the shapeof the channel;

FIG. 34A, FIG. 34B, FIG. 34C, FIG. 34D and FIG. 34E provide embodimentmethods for delivering light and/or implanting an intramedullary implantwithin the intramedullary space of a weakened or fractured bone;

FIG. 35 is an exemplary embodiment of one or more light fibers that arewoven into a contact form;

FIG. 36A and FIG. 36B illustrate exemplary devices for providing lighttherapy for treatment of the skin;

FIG. 37 illustrates the results of an experiment that shows wavelengthsof light that are shown to be antimicrobial against orthopaedic relevantbacteria;

FIG. 38A and FIG. 38B illustrate the results of an experiment thatdemonstrates a time-dependent killing of MSSA with the light at energylevels that are not toxic to mammalian cells;

FIG. 39A, FIG. 39B, FIG. 39C, FIG. 39D, FIG. 39E, FIG. 39F, and FIG. 39Gshow an experimental set up;

FIG. 40A, FIG. 40B, FIG. 40C, FIG. 40D, FIG. 40E, FIG. 40F, FIG. 40G,FIG. 40H, FIG. 40I, FIG. 40J, FIG. 40K, FIG. 40L, FIG. 40M, FIG. 40N,FIG. 40O, and FIG. 40P show the optical fiber (POF) experimental set up;

FIG. 41A is an exemplary graph that shows the spectral output from thefiber optic cable used in the device;

FIG. 41B and FIG. 41C show the blue light output from the site ofhumeral biopsy;

FIG. 42A shows an exemplary graph of the number of the patient isolatedMRSA culture counts versus time in seconds curing with the blue light;and

FIG. 42B shows the percent decrease in colony counts versus time inseconds curing with the blue light.

While the above-identified drawings set forth presently disclosedembodiments, other embodiments are also contemplated, as noted in thediscussion. This disclosure presents illustrative embodiments by way ofrepresentation and not limitation. Numerous other modifications andembodiments can be devised by those skilled in the art which fall withinthe scope and spirit of the principles of the presently disclosedembodiments.

DETAILED DESCRIPTION

Systems and methods for antimicrobial blue light photolysis (ABLP) forintramedullary treatment of bone infections and disorders are disclosedherein. In some embodiments, devices and methods including stabilizationand providing an anti-microbial effect for bone restructuring aredisclosed. An anti-microbial effect may also include a bactericidaleffect or an anti-bacterial effect, among other things. In someembodiments, the ABLP systems and methods can be used in conjunctionwith bone fracture fixation methods or other orthopedic procedures. Forexample, light for providing an anti-microbial, anti-bacterial effectcan be used in a variety of medical applications, including but notlimited to surgery, interventional radiology, respiratory and airwaymanagement, gynocology, dermatology, infectious diseases, wound care,and orthopedics.

Methods and systems for the controlled delivery intramedullary of bluelight (frequency about 380-500 nm) for the treatment of osteomyelitisvia a small diameter flexible fiber where the light is delivered in acircumferential fashion around the fiber, and where the energy deliveredfrom the fiber is of a same average intensity at the front end of thefiber as it was in the back end of the fiber. The methods and systemsdeliver intramedullary light to the canal over long lengths via a smalldiameter, minimally invasive pathway to a bone. The methods and systemsdeliver and maintain a light delivery system within the canal of thebone to provide single or multiple doses of the light, potentiallywithout removal of the light fiber system, thereby enhancing the ease ofmultiple treatments that may be required. In some embodiments, a portmay be created and the instrument for the application of lightredelivered into the canal. The controlled delivery of blue light infrequencies that can cause the death of the bacteria that causesinfections can be achieved. The use of light in the formation andtransfer of molecular oxygen on a cellular level, forming a reactivesinglet oxygen, where this oxidizing species can destroy proteins,lipids, and nucleic acids causing cell death and tissue necrosis. Themethods and systems provide secondary fluids, e.g., H₂O₂, that willenhance the death of the bacteria, wherein the blue light hasweakened/damaged the outer shell of the bacteria, and the O₂ from theperoxide accomplishes the final oxidation destroying/causing the deathof the bacteria.

System and methods for providing an anti-microbial effect on a bone aredisclosed. According to aspects of the disclosed subject matter, asystem for providing an anti-microbial effect on a bone includes adelivery catheter having an elongated shaft with a proximal end, adistal end, and a longitudinal axis therebetween, an inner void forpassing at least one light sensitive liquid, and an inner lumen, anexpandable member releasably engaging the distal end of the deliverycatheter, the expandable member capable of moving from a deflated stateto an inflated state by infusing at least one light sensitive liquidinto the expandable member, and a light conducting fiber sized to passthrough the inner lumen of the delivery catheter and into the expandablemember. In some embodiments, when the light conducting fiber is in theexpandable member, the light conducting fiber is able to initiatehardening of the at least one light sensitive liquid within theexpandable member to form a photodynamic implant and the lightconducting fiber is able to disperse light energy to provide ananti-microbial effect to the bone. The use of light to cure a monomercould be a secondary application of the system.

In some embodiments, the systems and methods described here can be usedfor the intermedullary treatment of orthopedic osteomyelitis, which isinflammation or swelling that occurs in the bone. Osteomyelitis canresult from an infection somewhere else in the body that has spread tothe bone, or osteomyelitis can start in the bone, often as a result ofan injury. Osteomyelitis is more common in younger children (five andunder) but can happen at any age. Osteomyelitis more commonly affectspeople younger than 20, or adults older than 50 years of age. Whilethere is a higher incidence of bone infections in adults that live indeveloping countries, hemodialysis patients, injection drug users, andpatients with certain chronic conditions such as diabetes are also moresusceptible to this infection. Bones can become infected in a number ofways, including through bacteria or an infection in one part of the bodythat may spread through the bloodstream into bone, or an open fractureor surgery, such as hip, shoulder or knee replacement surgery, that mayexpose bone to infection.

The systems and methods herein can also be helpful in the destruction ofbiofilm as the blue light can be used to break down the surfacebacteria.

ABLP can be used in a variety of procedures. In some embodiments, ABLPcan be used in minimally invasive surgical procedures. In someembodiments, ABLP can be used for the use and delivery duringintraabdominal procedures delivered via a trocar or cannula. In someembodiments, ABLP can be used for the use and delivery in arthroscopicprocedures delivered via a trocar cannula. In some embodiments, ABLP canbe used for the use in treating wound infections. In some embodiments,ABLP can be used for the use in the treatment of “open” surgicalprocedures.

A medical device disclosed herein may be used for treating conditionsand diseases of the bone, including, but not limited to, the femur,tibia, fibula, humerus, ulna, radius, metatarsals, phalanx, phalanges,ribs, spine, vertebrae, clavicle and other bones and still be within thescope and spirit of the disclosed embodiments.

Blue light has demonstrated antimicrobial properties against a range ofmicrobes, including but not limited to gram-positive and gram-negativebacteria, mycobacteria, molds, yeasts, dermatophytes, and similarpathogens. Antimicrobial blue light having wavelengths between about 400nm to about 470 nm can be used as alternative to antibiotics.

The basic electrodynamics of photosensitized reactions involves theabsorption of photons by the ground-state PS, causing electrons to bepumped to an excited singlet state. The excited-state PS can then engagein several different reactions that are destructive to microbes, such aselectron transfer reactions and the formation of radicals, including thepotent hydroxyl radical (Type I, redox reactions). A second activationpathway (Type II, peroxidation reactions) also exists, by which energytransfers via forbidden transition from the PS singlet state to anintermediate triplet state, a feature of only certain dyes likemethylene blue (MB). Because surrounding oxygen molecules are one of thefew biological molecules that exist in a naturally occurring tripletground-state, the oxygen can absorb, or “quench” the PS triplet stateenergy in a non-radiative exchange process. The oxygen molecules thenpump to their own singlet state forming highly reactive singlet oxygen.

Singlet oxygen is one of most powerful oxidative species known, and whengenerated in close proximity to bacterial membranes, rapidly results inmembrane perforation, protein cross-linking, and consequent cell death.It has been demonstrated that singlet oxygen can exert potent cytotoxiceffects on microbes without being internalized. The singlet oxygenlifetime in biological media is short, and this short active lifetimelocalizes the kill to the immediate vicinity of the activated molecule.

The most effective antimicrobial photosensitizers are positively charged(cationic) which permits them to bind to negatively-charged (anionic)microbial cell membranes. These cationic PS's bind poorly tozwitterionic (net neutral) human cells which are therefore protectedfrom damage (Loebel et al, 2016). The destructive reactions caused bysinglet oxygen are relatively selective for the organisms to which thePS adheres. The destructive effect is further amplified by the PDT“bystander” effect (Alexandre et al, 2007), a cooperative inactivationprocess between cells in a given microcolony, most likely mediated bymicrobicidal photoproducts or the transfer of lysosomal enzymes fromnearby cells. Broad-spectrum activity against viruses is rapid andpotent; here the active cidal mechanism involves diffusion-limitedpenetration across the envelope or capsid, followed by covalentcross-linking and destruction of side chains and backbone sites atmultiple positions on viral proteins; downstream chain reactions causingaggregation, altered conformation and directly oxidized guanosineresidues; and cross-linking, scission and irreversible oxidation of DNAand RNA with high second-order rate constant.

System Overview

According to embodiments of the present disclosure, the device, systemand methods disclosed provide, among other things, a site-specifictreatment approach to target a specific infection area within a bone.For example, in some embodiments, the site-specific treatment approachis designed to provide treatment in the endosteal, i.e. inside surfaceof the bone, so as to treat infection in the bone from the medullarycanal, i.e. from the inside to the outside. This is contrast totreatments using antibiotics to fight infection; the treatment used ofantibiotics results in a systemic broad approach towards treating theinfection, which is not a targeted site-specific treatment as per theinstant disclosure. For example, after an invasive surgical procedure aninfection may develop in the patient, requiring the patient to undergoantibiotic treatment. Treatments using antibiotics are delivered eitherorally or by infusion, wherein such broad treatment goes towards anentire anatomical treatment of the body. For example, even during thecourse of this broad treatment using antibiotics, the specific area ofthe actual infection may not be properly treated and/or as a result thisbroad treatment likely will deliver more drugs than is required to treatthe specific infection area or mall area. The present disclosure isdirected to a site-specific approach by applying light to the specificinfection area to kill the infected matter or bacteria. In someembodiments, the present disclosure can result in providing directtreatment to an infection area, using only an amount of treatmentnecessary to kill the infection, i.e., which is in contrast to the broadtreatment approach of using antibiotics. In some embodiments, the use oflight to treat an infection can result in only an additional smallamount of antibiotic as a “clean-up” that may be required. In someembodiments, at least one aspect of the site specific treatment resultsin a faster “kill” or termination of the infection versus the broadtreatment approach of using the systematic drug, i.e. antibiotics.

In some embodiments, the device, systems and methods disclosed providean anti-microbial effect on and/or in bones. In some embodiments, thedevice, systems and methods disclosed herein can provide ananti-microbial effect for orthopedic procedures. In some embodiments,the device, systems and methods disclosed herein can provide abactericidal effect on and/or in tissue or bones and surrounding tissue.In some embodiments, the device, systems and methods disclosed hereincan provide an anti-bacterial effect on and/or in tissue or bones andsurrounding tissue. In some embodiments, the device, systems and methodsdisclosed herein can provide an anti-infective effect on and/or intissue or bones and surrounding tissue. In some embodiments, the device,systems and methods disclosed herein can provided an anti-fungal effecton and/or in tissue or bones and surrounding tissue.

In some embodiments, the device, system and methods disclosed providefor an application of light to kill the infection which creates theformation and transfers energy to molecular oxygen, thus forming thereactive singlet oxygen. This oxidizing species can destroy proteins,lipids, and nucleic acids causing cell death and tissue necrosis. Theinstant disclosure's application of light creates molecular oxygen, thusforming the reactive porphyrins. For example, during treatment,electromagnetic radiation having wavelengths in the visible spectrum(i.e., visible light above 395 nm, by non-limiting example) reacts withnaturally produced and/or concentrated “endogenous” chromophores(porphyrins). At least one effect of the application of theelectromagnetic radiation (illumination) is that the light inconjunction with or in combination with the porphyrins produces necrosisor cell death to the bacteria as evidenced by the microorganism'sinability to divide. It is noted that the application of treatment ofthe instant disclosure provides treatment without the addition ofancillary drugs or chemicals, which can be considered as a “holistic”killing treatment or approach to fighting infection.

As a light-based disinfection approach, antimicrobial blue light (aBL),particularly in the wavelength range of 400-500 nm, has an intrinsicantimicrobial effect. Compared to traditional photodynamic therapy, aBLtherapy excites the endogenous chromophores of bacteria, and thus doesnot require the addition of exogenous photosensitizers. Furthermore, incomparison to ultraviolet irradiation, aBL shows much less detrimentaleffects in mammalian cells. The bactericidal activity of aBL isnon-specific, and many microbial cells, including various antibioticsresistant strains, are highly sensitive to this treatment. aBL therapyhas previously shown promise as a treatment for various clinicalpathogens, including, but not limited to Pseudomonas aeruginosa,Acinetobacter baumannii, methicillinresistant Staphylococcus aureus(MRSA), and Candida albicans, and other pathogens.

In some embodiments, the device, system and methods disclosed providefor an application that can be used as a self-standing instrument to“wand” the canal of the bone or as a part of a balloon (with monomer) toboth stabilize and kill the infection, i.e. providing a site specifictreatment approach. The transparency of the monomer increases as it isilluminated with light, allowing more light therethrough. It is possiblethat treatment for an infection within a canal of the bone may onlyinclude using a balloon placed within the canal and merely introducingthe application of light disclosed in the present disclosure to treat orkill the infection area. For example, the use of the balloon can provideat least one benefit, in that the expanded balloon acts as filler withinthe canal compressing and causing the remaining medullary canalmaterials to be displaced and putting the balloon in direct appositionto the medullary canal wall. Whereby, the results of the application ofthe balloon within the medullary canal allow for an environment for anappropriate transmission or application of light to kill bacteria in theinfection area. For example, failure to displace the medullary canalmaterials would result in an occluded canal, which would be preclusiveto light meeting the bone walls or endosteal surface, thus failure intreating the infection area.

Further, the use of light in accordance with the present disclosure canprovide for the termination of newer and more virulent strains of drugresistant bacteria, i.e. “super bugs”. Traditional antibiotic methods ofkilling infections using antibiotic fails to kill virulent strains ofdrug resistant bacteria, i.e. super bugs. Traditional antibiotic methodskill using a chemical and biologic response associated with O2, i.e.necrosis and cell inability to divide and replicate. As noted above, thepresent disclosure incorporates the application of light which causesthe formation of porphyrins, wherein the application of electromagneticradiation (illumination) in conjunction with or in combination with theporphyrins, produces necrosis or cell death to the bacteria as evidencedby the microorganism's inability to divide. Further, as noted above, theapplication of electromagnetic radiation (illumination) according to thepresent disclosure presents a treatment of the infection area frominside the bone to outward.

In some embodiments, the light intensity will be uniform over the entirelength of the one or more optical fibers used to deliver the blue lightto the treatment site. This can be achieved, for example, by removingthe cladding in specific configurations such that the intensity of lightthat is passed to the tissue through the areas of the fiber withoutcladding is uniform along the entire length thereof, as will beexplained in more detail below. In some embodiments, this allows lightto be emitted down the entire length of the fiber from the side of thefiber to treat any length of tissue.

Illumination Providing an Antimicrobial Effect within Cavities of theBone

FIG. 1A, FIG. 1B, FIG. 1C, FIG. 2A, FIG. 2B, FIG. 2C and FIG. 2D areschematic illustrations showing various components of an embodiment of asystem 100 of the present disclosure. As shown in FIG. 1A, the system100 includes a light source 108, a light pipe 120, an attachment system130 and a light-conducting optical fiber 106 having a nonlinearlight-emitting portion 158, which emits light from the outside of theoptical fiber 106 along its length. The attachment system 130communicates light energy from the light source 108 to the optical fiber106. In some embodiments, the light source 108 emits frequency thatcorresponds to a band in the vicinity of 350 nm to 770 nm, the visiblespectrum. In some embodiments, the light source 108 emits frequency thatcorresponds to a band in the vicinity of 380 nm to 500 nm. In someembodiments, the light source 108 emits frequency that corresponds to aband in the vicinity of 430 nm to 450 nm. In some embodiments, the lightsource 108 emits frequency that corresponds to a band in the vicinity of430 nm to 440 nm.

The system 100 includes emitting a beam of a blue light or violet-bluelight within a cavity of the bone via an optical fiber for bothilluminating towards polymerization as well as towards providing anantimicrobial effect. For example, light from a light source can be usedto kill micro-bacteria located within a cavity of a bone before, duringand after the healing process of the fractured bone. Steps to kill themicro-bacteria in the cavity of the bone can include emitting the beamof blue light or violet-blue light having a wavelength from about 380 nmto about 500 nm. For example, in some embodiments, broad spectrumvisible light in the range of 400 nm-480 nm can be used. In someembodiments, the light can be generated via a metal halyide bulb, orfrom a specific frequency LED. In some embodiments, broad spectrum lightfrom 380 nm to 480 nm, inclusive of a small component of UV, can beused. In some embodiments, single spectrum light can be used, i.e., theuse of specific frequency LEDs tuned to those frequencies that are knownto be specific to certain bacteria. For example, in some embodiments,the blue light/beam can have a wavelength of about 405 nm, about 420 nm,about 450 mm, about 460 nm, or about 470 nm, or any other wavelengththat can damage various bacterias. In some embodiments, multiple singlespectrums can be used, e.g., 405 nm and 420 nm. The individualfrequencies of light can be mixed/focused to provide two or morefrequencies within a single fiber. For example, in some embodiments, theblue light/beam can have a wavelength of about 405 nm, about 420 nm,about 450 nm, or about 470 nm.

In some embodiment, more than one LED, such as dual LEDs can be used.This can potentially increase in power as LEDs have a defined amount ofpower in watts/milliwatts. If more power is required to achieve theantimicrobial effect, the ability to combine more LED illumination powercan be useful. The LED illumination can be directed though the use ofmirrors, prisms or other optical pathway modifiers that can be broughttogether, focused and directed through the fiber.

The other rationale for the use of multiple LEDs is selectingfrequencies that are known to have an antimicrobial effect on thespecific microbial target. It has been shown that some bacteria can beremediated with specific frequencies, while other bacteria are notaffected, or are affected at lower levels. Through the ability ofmerging multiple light frequencies, the user can either pick theappropriate light for the bacteria or can apply multiple frequencies toremediate the bacteria.

Still referring to FIG. 1A, it is contemplated the light source caninclude a single bulb or multiple bulbs. For purpose of clarity, bulb isused as an indiscriminate description of a light source. A bulb may be ametal halide source, a mercury or xenon incandescent or LED. The type oflight source can vary, and can be in the form of one or more LEDs, alaser, or any other potential light source that can provide the desiredwavelength of light. The light source may further include one ormultiple ports to attach light fibers. The light fibers or light guidesmay be joined, mixed or include some combination thereof, within thesystem. Depending upon the application, the light source can be designedto provide higher outputs in different frequencies, i.e. using multiplebulbs, so as to overcome potential fall off aspects that may occur usinga single bulb. If multiple bulbs are used, it is contemplated that theremay be multiple types of bulbs used in the system. For example, eachdifferent type of bulb may provide a specific attribute to meet anintended design aspect for the particular application, which may includeattributes relating frequency ranges, energy density ranges, operationlife expectancies, etc. Further, regarding other elements within thesystem where multiple elements of the same element are used, i.e. lightfibers (optical fibers, light guides, etc.), light conductive materialsand the like, it is contemplated that there may be different types ofthe same element used within the system. As noted above, each differenttype of element may be used depending upon the specific attribute tomeet an intended design aspect for the particular application, which mayinclude attributes relating material type(s), performance relatedranges, operation life expectancies, etc. In conjunction with choosing aspecific element, any materials and elements used with that specificelement may be further used, so as to meet the intended planned designfor the particular application. For example, it is contemplated a clearliquid epoxy may be used to bind and fill in interstices of multiplefibers towards a smooth tube or the like, with the system.

In some embodiments, there can be multiple light sources coupled todifferent components of the system. For example, a first light sourcecan be coupled to the proximal end of one or more fibers, and a secondlight source can be coupled to the distal end of the one or more fibers.

In some embodiments, a metal halyide bulb can be used. As shown in theexemplary graph in FIG. 3A, the waveform provides “peaks and valleys”such that specific spectrums are naturally higher than others as afunction of the bulb/light that is illuminated from the bulb, but theintensity of the specific frequencies within the waveform cannot bechanged. Looking at the power of the various frequency bands as apercentage of the total power delivered, it is shown that most of thefrequencies outside the 400 nm-500 nm range are fairly low in powerpercentage-wise.

If a specific frequency/intensity is needed to affect the kill of thebacteria and that intensity is lower than needed, there is no means toincrease the power without raising all the other frequency powers. Thisruns the risk of potentially inducing more power than is required and atthe risk of potential damage to normal cell viability.

As shown in FIG. 4A, FIG. 4B, and FIG. 4C the frequency of the systemscan remain the same while the power can increase, and the step up inpower can result in faster and better kill of the target bacteria. Thus,more power results in more a more effective bacteria elimination.Similarly in FIG. 4D and FIG. 4E, which illustrates exemplary graphsshowing time versus bacteria reduction at different power settings, highpower correlates to an increase in bacteria reduction. Three differentpower level are shown in FIG. 4D, with lines 390, 391, 392 going fromlowest to highest power. Similarly, three different power level areshown in FIG. 4E, with lines 393, 394, 395 going from lowest to highestpower.

A plurality of specific LEDs at the specific frequencies can be used atfrequencies that are desired or needed to cause an antimicrobial effect.This allows the frequency and the intensity delivered to the tissue ismore defined and specific as the intensity of each LED is controlled—thedelivered intensity at the various frequencies can be the same ifdesired—vs the peaks and valleys of the metal haylide.

If specific frequencies of light are appropriate in the remediation ofone bacteria, while other frequencies are not, those frequencies can beturned off as there is no reason to deliver light to the treatment zoneif it is not beneficial. Thus, it is possible to provide the desiredfrequencies of light using a subset of the plurality of LEDs as neededfor each specific bacteria. This can provide a variable and tunablesystem.

The “tuning” of the system is relegated to the application or use ofspecific LEDs as each LED is a single frequency light. Thus, the systemdoes not have the ability to adjust the LEDs other than adjusting thepower intensity up or down. The system uses the combination of theavailable LEDs to create an appropriate blend of frequencies to achievea blend of light frequencies to achieve the appropriate kill factor fora given bacteria. The system can adjust the power to increase ordecrease the peaks (i.e., power intensity) of the various frequencies.In some embodiments, this can be done to ostensibly derive a square waveto create a block of power hitting the bacteria.

For example, as shown in the exemplary graph in FIG. 3B, 5 LEDSs can beused at 405, 415, 435, 450 and 475 nm. A power grid of the spectrum fromthe 5 LEDs is shown in FIG. 3C. In some embodiments, individual powerfor each LED can be adjusted so each LED spectrum has its peak at thesame level. FIG. 3D illustrates an adjustment of the power levels ofthree of the five LEDs such that the peak is approaching similar heightson the illustrated graph. As shown, the LEDs running at 415 and 450 areturned off. As shown, the three peaks have roughly the same peak eachwith the same power. This can be done such that each LED gives out thesame power. If more power is needed, they can be adjusted individuallyor serially so that none of them become overpowered. It will beunderstood that any number of LEDs can be used and defined for anyfrequency. All the LEDs can be running at the same power or turned offif any of them are not needed. For example, if a specific bacteria isaffected by a certain frequency, only that LED at that desired frequencycan be run while the others are turned off. Thus, a fully variable anddynamic LED array can be used that can be customized depending on thedesired treatment. In addition, any variation between 400 nm and 475 nmcan be used.

In some embodiments, the system can be used and controlled either prioror during the procedure, and has the ability to vary/modulate/alter theintensity and/or the frequency of the light being delivered to treattissue. The use of a “blue light” can cause cellular death, for examplein the range of 400 nm-470 nm, absorbed by porphyrins, causing celldeath by the generation of toxic reactive oxygen. The bactericidaleffect of blue light has been shown in many pathogenic species withvarying energy doses of J cm-2 sufficient to achieve remediation.

FIG. 5 illustrates an exemplary graph showing the use of five LEDs andtheir effect on various bacteria. For example, as shown, E. coli had a˜4 log reduction with the 5 LED system, and ˜0.6 log reduction with thebroad spectrum.

It will be understood that both frequency and power are responsible forthe killing of bacteria. In some embodiments, the frequency and/power ofthe plurality of LEDs can be tuned in an attempt to target specificbacteria. In some embodiments, a more broad spectrum approach can beused with the plurality of LEDs. For example, using high power at(seemingly) the wrong frequency can provided a null response. Inaddition, as many physicians do not know the specific strain of bacteriathat is affecting a patient, the effects of using a broad spectrum lightsystem can outweigh negatives of frequency specificity in an attempt totarget a specific bacteria.

In some embodiments, a plurality of LEDs, as shown in the exemplarygraphs in FIG. 6A and FIG. 6B, can be used and can be dialed in via alight box (i.e., switches thrown to pull specific frequencies), and theability to drive the various LEDs at different powers (so that theoptical output is the same). This allows for “ganging up” of multipleLEDs with different frequencies, and optical mirrors can be used tomerge the multiple light frequencies into a single plastic opticalfiber. Different LED frequencies can have different optical output,e.g., intensity. The output can be adjusted through the drive current,where overdriving them will result in higher optical output. Themultiple LEDs ganged up can be used to fine tune thefrequency/frequencies of light that are delivered to the fiber in thetreatment of the bacteria, as certain species of bacteria have differentfrequencies of light that are able to kill them. This allows the systemto target the light to the species of bacteria to make it a moretargeted system.

The peaks shown in the exemplary graphs in FIG. 7A, FIG. 7B, FIG. 7C,and FIG. 7D are from different LEDs. In some embodiments, more than oneLED (or any light source, such as lasers) can be used to provide lightto the same light fiber. For example, 1 LED, 2 LEDs, 3 LEDs, 4 LEDs, 5LEDs, 6 LEDs, 7 LEDs, 8 LEDs, 9 LEDs, 10 LEDs, 12 LEDs, or 15 LEDs ormore than 15 LEDs can be used depending on the desired spectrum of lightdelivered. It is possibly to use two or more LEDs to provide more power.Intensity of power delivered across delivered light spectrum can be madeuniform or substantially uniform by adjusting the current (power) ofeach LED. Additional LEDs can be added to fill in gaps so a user cancreate and control the light spectral curve delivered by a plurality ofLEDs. For example, there can be uniform power across the spectrum, powercan be varied across the spectrum, and the addition of additional LEDsadjusts the spectral curve.

FIG. 7A, FIG. 7B, FIG. 7C, and FIG. 7D illustrate various exemplarygraphs showing the spectral curves of the presently disclosed device andmethods having varying plurality of LEDS. FIG. 7A illustrates theexemplary spectral curves of the presently disclosed device having 15LEDs or more LEDs. FIG. 7B illustrates the exemplary spectral curves ofthe presently disclosed device having 12 LEDs or more LEDs. FIG. 7Cillustrates the exemplary spectral curves of the presently discloseddevice having 8 LEDs. FIG. 7D illustrates the exemplary spectral curvesof the presently disclosed device having 4 LEDs.

In some embodiments shown in FIG. 8 , FIG. 9 , and FIG. 10 , one or moreconical reflecting members (e.g., cone mirror) with an LED mounted onthe tip of the reflective cone can be used such that the incidence ofreflection causes a circular dispersion of even light around the cone. Acone mirror 410, as shown in FIG. 8 , can be used in combination with anLED 412. The angle of the taper of the cone mirror can be used to directthe reflective beams of light outward, as shown with the cone mirror 414and LED 416 of FIG. 9 . This combination of LED and reflecting membercan create a radiant ring of light due to the shape of the reflectingmember.

In some embodiments, a plurality of LEDs 418 can be connected togetheron a string or fiber 420, as shown in FIG. 11 , to form a chain of LEDs.The string of LEDs can produce even light deposition over the length ofthe string. Any length of string can be used and any number of LEDs canbe position therealong depending on the size and shape and location ofthe treatment site.

In some embodiments shown in FIG. 10 , a plurality of sets of conicalreflecting members 400 a, 400 b, 400 c, 400 d and LEDs 402 a, 402 b, 402c, 402 d are positioned in or encased within a clear tube 404 topreclude the transmission of light by intramedullary fluids in contactwith the reflection or emitter faces. Support spacers 406 a, 406 b, 406c, 406 d can be positioned between each conical reflecting member andLED to allow for rotation and malleability of the assembly. The stackedLEDs and cone mirrors within the tube act as a light fiber of LEDs.

In some embodiments, a malleable rod can be used comprised of multipleLED's mounted to the ends of small sections of high efficiency glasscoupling (LED-glass-LED-glass) where the glass sections are internallymodified to cause the light from the LED to be deflected outwards. Theemitter face of the LED's can be mounted on top of a reflective mirroredshape to eminate the light outwards. These are encased within a cleartube to preclude the transmission of light by intramedullary fluids incontact with the reflection or emitter faces.

As shown, cone mirrors can be mounted on a surface that allows them tobend/rotate. An apex of the cone mirror can meet or be affixed in aposition relative to the LED emitter such that it takes the light fromthe emitter and disperses it radially outwards. These assemblies can bestacked, multiple ones on top of each other, to form a line or acylinder of emitters and cone mirrors. The entire assembly can be placedwithin a thin clear transparent tube which prevents bodily fluids fromcoming in contact with the emitter and/or the cone mirrors, which wouldpreclude light transmission. The mirrors are used to bounce the lightoutward as the LED directs the light down the fiber. The geometry of themirrors (flat planes) help in achieving this circumferential outwardredirection of the light. The cone mirrors are affective in shortlengths, allowing for a system that can be flexible as the cone mirrorscan be bent in reasonably short segments.

Various treatment protocols can be used when treating a bone infection.In some embodiments, the ABLP for single stage delivery can be used fortreatment of infection (e.g., one dose of light—on/off) for some definedperiod of time, after which the catheter can be removed from the canal.In some embodiments, the ABLP dual stage can be used for longer termtreatment, with the catheter residing within the canal for a long periodof time, for example a period of days. This can provide multiple dosesof light to the canal, which allows for longer term indwelling of thecatheter. The ability to place a port 430 through a bone surface 434,with access to the intramedullary canal, to open the port and deliverthe light fiber 432, remove the fiber and close the port, and then openthe port in a different time period and deliver a new fiber foradditional treatments, as shown in FIGS. 12A and 12B. The port 430 caninclude a septum 436, an antimicrobial disk (or bandage) 438, a flexibletube 440 through the bone surface, and an opening 442 through one ormore fibers can enter the bone. FIG. 12B illustrates an embodiment ofthe port 430 for delivering the fiber and can provide a way to maintainthe position of the fiber. In some embodiments, the ABLP can be used asa single fiber, where only a single fiber is delivered within the canalproviding light to the infected area. In some embodiments, the use ofthe ABLP as multiple fibers delivered within the canal such that all ofthe fibers providing light to the infected area is used. In someembodiments, multiple fibers can be used, each providing individualfrequencies of light. In some embodiments, multiple fibers can be used,each providing multiple spectrums of light. In some embodiments, thedelivery of the multiple fibers within the canal can be either as asingle treatment, or the multiple treatments, as mentioned above.

Still referring to FIG. 1A, the beam of blue light/beam can delivervariable energy densities to bone walls of the cavity of the bone.However, unlike systems that have an illuminator directly or integrallypart of the light source, there is no heat generation through thedelivery of light using the catheter, for example to bone walls of thecavity of the bone, while emitting the blue light/beam. The steps ofemitting the blue light/beam within the cavity of the bone may becompleted without: (1) exposing the bone walls to further evasivesurgical procedures due to antimicrobial effect related treatments; (2)the need for applying antimicrobial type liquids or relatedapplications; and (3) the need of removing the killed micro bacteriafrom the affected area. Micro-bacteria may be defined, by non-limitingexample, as an opportunistic microorganism. For example, a bacterium,virus, fungus or the like, that takes advantage of certain opportunitiesto cause disease, i.e. those opportunities can be called opportunisticconditions. These microorganisms are often ones that the human immunesystem cannot raise an adequate response, such these microorganisms caneventually overwhelm the body's weakened defenses.

For example, according to at least one aspect of the disclosure, it iscontemplated to kill micro bacteria that may have an opportunity toexist or already exists within the cavity of the bone. The use of theblue light/beam can include many variables when treating an affectedarea, by non-limiting example, the blue light/beam may incorporate manycombination of aspects when being applied to an affected area such as:(1) variable energy densities, conceptually by altering the wave form onthe light liber it is possible to emit more or less light in differentand specific areas—and similarly alter the temperature on a local levelor site specific area; (2) variable generated temperature(s) at aspecific location within the affected area; (3) variable exposure timeemitted to the affected area; (4) variable distance of the opticalfiber's distal end to the affected area; and (5) a puking or constantblue light/beam emitted or a combination thereof, among other things.

Still referring to FIG. 1A, the instant disclosure may additionallyinclude step or steps of incorporating variable temperatures such ascooling an affected area (before, during or after treatment), so thatthe bone wall temperature along the blue light/beam emission does notexceed a temperature that may result in irreversible damage to the bonewalls of the cavity of the bone. It is contemplated that possiblycooling vents may be used in the process so as to pulse a coolingliquid, i.e. water, through channels to cool the implant and thesurround tissue. It is also possible that to fill the balloon with asuper cooled material so as to necrose or freeze the biofilm, i.e.bacterial colony, through an overall thermal effect and in conjunctionwith the blue light. By non-limiting example, the bone wall temperaturealong the blue light/beam emission may be contemplated not to exceed atemperature of about 42° C. or between 40° C. to 45° C. It iscontemplated that a super cooled device may be used so that theapplication necroses tissue.

Further, the energy emitted by the blue light/beam may be termed inportions of joules (i.e. radiant energy), joules per cubic meter (i.e.radiant energy density), watts (i.e. radiant flux), watt per meter andwatt per hertz (i.e. spectral flux), watt per steradian (i.e. radiantintensity), or the like. In some embodiments, the light that isdelivered from the system from the tips of the fibers is measured inmilliwatts or watts of energy. When the system is run, the seconds thatthe system is emitting light is multiplied by the milliwatts/watts tofind the Joules (power).

The radiant energy (light dispersion of the light fiber) is evenlydispersed over the length of the active fiber, both longitudinally andcircumferentially. Therefore the power is dispersed over a greater area,albeit at lower individual measurements associated with the greatercoverage area. This even dispersion of power allows larger areas to becovered without fear of potential over illumination/overpowering thetissues. While greater power is needed to achieve the resultant energybeing transmitted evenly along the length of the fiber, the process isfar more controllable, owing to the greater area, versus that of asingle point emitter.

It is noted that when using light to kill bacteria, it can be dependentupon a variety of factors, not the least of which, may be intensity asdefined by joules (watts) or intensity multiplied by time. Further, thepolymerization and antimicrobial effects are not the same, i.e., at thesame time, or dependent such that, where polymerization can be themarriage of a known frequency light to a known monomer, i.e., photoinitiator, with a specified time toward polymerization, the successfulability to kill bacteria may require a higher energy deposition thanwould be required to cure. It may be possible to circumvent a need toapply non-clinically relevant times, more light, i.e. energy that mayneed to be applied. Among other things, a possible solution may be toattempt to use higher energy and illumination sources. The use of higherenergy sources, or potentially more focused and specific wavelengths,may obviate the limitations in the transference and limitations to theamount of energy may be transported down the fiber. The issue related totransference appears when light is transferred using a large/long activelength of the fiber as there are inherent and physically unavoidablelosses in transmission. At each point of emission there is a loss-oflight that increases incrementally along the length of the fiber. Eachfurther point starts with less light than the point before and decreaseslight at the next point such that at some point forward, there will beno emission as all the light has been consumed prior to the end of thefiber, creating a downward slope of light emission.

The optical fiber 106 used in the system 100 can be made from anymaterial, such as glass, silicon, silica glass, quartz, sapphire,plastic, combinations of materials, or any other material, and may haveany diameter. Further, the optical fiber 106 can be made from apolymethyl methacrylate core with a transparent polymer cladding. Itshould be noted that the term “optical fiber” is not intended to belimited to a single optical fiber but may also refer to multiple opticalfibers as well as other means for communicating light from the lightsource to the expandable member. It is possible the fibers, afterexciting the light source, may be twisted so as to form into a singlefiber. Further, the optical fiber may comprise of a single fiber at alocation that is in combination with multiple fibers at anotherlocation. It is possible, the multiple fibers positioned at the otherlocation may be further incorporated into another single fiber at yet atanother location within the system, i.e., the method of using the lightfiber may be a single fiber or multiple fibers or any variation thereof.

If a prescribed dose (for example, intensity or some other measurementassociated with the light) is defined as the means to achieve anantimicrobial effect, then that dose/amount of energy needs to bedelivered over the entire length of the fiber for the affected area tobe treated (except in the case of an infection being confirmed to asingle location where illumination can be directed similar to the effectof a flashlight or spotlight).

For example, bones are hollow and often in the form of long linear tubessuch that an infection can run the length of the bone. Equal energy canbe applied to the affected length. Without an even energy delivery, onearea of the bone could be getting a great intensity than other areas, sothe bone is not being medicated evenly.

In some embodiments, it is possible to define a specific energy that isrequired to remediate a specific bacteria. This can include the energyemitted by the fiber, and a time of the exposure. This can be used todefine the joules required to kill a bacteria. As the treatment of boneoften involves the treatment of elongate tubular areas, the delivery ofthe fiber down the length of the bone requires that the illumination isnot only even over the length of the fibers, but also even in acircumferential manner. Thus, in some embodiments, the light is not onlydelivered evenly in a single angle off of the fiber, but is alsodelivered evenly or equally in a circumferential manner.

This method of delivering light along the length of bone or otherinfected area overcomes the issue of decreased energy deposition overlength of a fiber.

In some embodiments, this can be achieved by the manner in whichcladding is removed from the fiber. Cladding is a bonded material on thesurface or outer diameter of the fiber to maintain internal reflectanceand transmission of the light down the length of the fiber withoutlosses (attenuation) by light escaping from the fiber. For example, whena small opening, such as a nick, is made in a proximal end of thecladding, the light blasts out of that opening and steals light from thearea below the nick. Each subsequent “nick” bleeds out light but theintensity of the second nick is less than the first as the pressure hasalready been lowered. This continues until the energy is almostnegligible at the distal end, as shown in FIG. 3D.

Failure to have a system that maintains even light energy or dispersionof the system over the length of the fiber can cause a differential inenergy delivery. The inbalance then precludes a method to achieve adelivery system where the specified power delivery is even over thelength of the device. For example, either one end of side of the deviceis overpowered or underpowered. Thus, changing the power would lead toan unbalanced system.

The light delivered by the fiber needs to be even over the length of thefiber such that the correct power over the length of the fiber can beprovided, at even powers at short lengths over the fiber to achieve theantimicrobial effect, as shown in FIG. 13 . If there is an imbalance inthe power over the length of the fiber, there can be high spots and/orlow spots, and the patient suffers as there isn't any way to achieve abalance in treatment. If there are high spots and/or low spots (areas ofincreased intensity and/or areas of decreased intensity), then there isnot even power deposition to the targeted area needing treatment. Thiswould correlate to overmedication or undermedication of the treatmentsite. Thus, the correct power can be selected for an even powerdistribution over the length of the fiber.

In some embodiments, uniform light delivery along the length of a fibercan be achieved by virtue of a variable helical spiral. Removal ofcladding in this manner allows the system to maintain the same energydeposition over the length of the fiber such that the top and the bottomare even and light emanating from all planes of the fiber are uniform.This allows for 360 degrees of light over the length of a fiber.

The type of light fiber can vary, and can include traditional fiberoptics, telecommunication fiber, or plastic fiber optics that can beefficient in the transmission of light with minimal light loss. Itshould be noted that with any form of diffusing/diffusion light fiber,the intensity of the light will decrease over length of the fiberdependent upon the amount of light being diffused (length and/or area).

A process of even diffusion of the light in the cladding over the lengthof the fiber results in stronger intensity at the initiation end of thefiber and an ever decreasing amount as distance is increased from theinitiation source. This reduction in optical power and intensity negatesit's use in the curing of photodynamic implants, as the intensity at thedistal end has weakened significantly (or the increased power to achievecuring at the distal end of the fiber has been increased sosignificantly that there is an overpowering of the fiber at the proximalend). Thus, a variable helix of a cut in the cladding, spiraling downthe fiber, with the spiral getting tighter and tighter as the light isbleeding out allows for even light dispersion over the length of thefiber.

In some embodiments, an antimicrobial system can include an opticalfiber having a diameter in the range of 1 mm to 20 mm, with a lightemitting helical coil on the circumference of the fiber. Theillumination of the fiber is delivered radially from the fiber outwards.Illumination frequencies are in the visible spectrum from about 400 nmto about 475 nm.

Thus, in some embodiments, a fiber 450 can have a spiral/helical coil ofcladding that can be removed, allowing light to escape from within thefiber to affect the ABLP process, as shown in FIG. 14A and FIG. 14B. Thecladding is removed such that the light intensity along the length ofthe fiber is uniform. Traditionally, PMMA (acrylic) comprises the core(96% of the cross section in a fiber 1 mm in diameter), and fluorinatedpolymers are the cladding material. Since the late 1990s much higherperformance graded-index (GI-POF) fiber based on amorphous fluoropolymer(poly(perfluoro-butenylvinyl ether), CYTOP) has begun to appear in themarketplace. Polymer optical fibers are typically manufactured usingextrusion, in contrast to the method of pulling used for glass fibers.

In some embodiments, cladding is removed physically (i.e., scratchingthe surface in a very precise method using, for example, a diamondtipped cutting head, a razor, or scalpel blade) which can reveal thefiber and allow light to emanate through the space in the cladding. Insome embodiments, cladding is removed chemically from a polymer opticalfiber using organic solvents which can also be used to create etchedportions of the fiber allowing the attenuation of light. Cladding canalso be removed using low energy lasers to finely ablate the surface,water jet cutting, or with compressive dies to penetrate/break thesurface of the cladding.

To provide for uniform light delivery, when the cladding is removedalong the length of the fiber, the spiral can tighten as it progressesfrom a proximal end of the fiber to a distal end of the fiber. In someembodiments, the depth of the cut into the fiber can also increase fromthe proximal end of the fiber to the distal end of the fiber.

The greater penetration depth of the fiber towards the dispersion oflight requires increased penetration depth as the light intensity alsodecreases through the attenuation or loss of light though the removedcladding area.

For example, a spiral design, as shown in FIG. 15A, FIG. 15B, FIG. 15C,and FIG. 15D, can be used that wraps around the fiber on the line of thespiral, where the cladding has been removed to allow light to escape. Asthe light escapes, the intensity of the light being emitted is reducedfrom 100% of the light at a proximal end of the fiber closest to a lightsource, and the light moves distally further and further down thespiral, there is less light coming out of the fiber (the light intensitydecreases). In order to resolve the issue, the pitch can be increased tonarrow the gap between the two spirals and to increase the amount oflight hitting the target. However, as the light moves further andfurther down the fiber and the intensity is dropping, the depth of thecut in the cladding can be increased to decrease the distance that thelight within the fiber needs to transit before exiting the fiber. Thus,in order to achieve the necessary amount of light along the entire fiberlength, there is a balance of the spiral and the depth of the claddingcuts to achieve an even light distribution over the length of the fiber.For example, an initial cut in the fiber can be shallow such that onlythe cladding is removed. The cuts can become deeper distally along thelength of the fiber (i.e., thousands of an inch deeper).

In some embodiments, the cut in the cladding can also vary in depth,with the proximal aspect of the fiber cut only a minimal depth (forexample, ˜10 micron depth) to allow the light to pass through to anincreasing depth of cut as the spiral moves down the length of thefiber. This is illustrated in plots based on pitch (mm), cutter rpm andcutter amps, with the increased amps yielding a deeper cut.

In some embodiments, the removal process includes holding the fiber in arotary chuck with the cutting point mounted on a motor. A springposition can be used to advance the pointer and make contact with thecladding, and the spring drive holds the pointer in contact with thefiber. While the increased pitch and cutter rpms are applied, the cuttersystem is rotated around the fiber to apply the spiral cut (as does theincreased depth of the cut), as shown in FIG. 16 . As shown in FIG. 16 ,there is an increasing helical pitch, including a slow/shallow pitch atthe proximal end and a very tight pitch at the distal end. It will beunderstood that the pitch becomes tighter from the proximal end to thedistal end of the fiber. Further, the depth of the cut increases as thecut progresses down the length of the fiber from the proximal end to thedistal end.

In some embodiments, the cladding is removed from only certain portionsof the fiber. In some embodiments, the cladding is removed 360 degreesaround the fiber. In some embodiments, the cladding is only removed in a180 degree orientation, as shown in FIG. 17 , with the cut sideoutwards. As shown in FIG. 17 , the uncut side of the fiber 450 can bepositioned against a balloon 452. The 180 degree cut side is exposed tothe endosteal surface. By having the spiral cut only on 180 degrees ofthe fiber, the intensity of the light increases. The reduction in thecut cladding can increases the output efficiency. In some embodiments,the cladding is removed in a 90 (45+/−) degree orientation, with the 90degree cut side exposed to the endosteal surface. This reduction in thecut cladding can also increases the output efficiency. In someembodiments, the cladding is removed in a 120 (60+/−) degreeorientation, with the 120 degree cut side exposed to the endostealsurface. The reduction in the cut cladding can increase the outputefficiency. It will be understood that any amount of the circumferenceof the cladding can be removed from the fiber to control the amount oflight from the fiber and the area of tissue being exposed thereto. Thecladding can be removed in the direction of intended light delivery.

Based on cladding removal, as shown in FIG. 16 , energy dissipationremains the same or substantially the same as length increases. Claddingcut width is same, but the depth of cut increases over the length solight emanates stronger toward the distal end. A helical spiral can becut with a slower pitch at proximal end, and the pitch can increase asit moves toward the distal end, creating a tighter spiral.

In some embodiments, rather than removing a portion of the cladding fromthe fiber to achieve uniform light energy delivery/power depositionalong the length of the fiber, one or more fibers can be used to deliverthe light energy uniformly does not include cladding. When using a fiberwithout cladding, the fiber can be overcoated with a light diffusingmembrane. The over coating can be applied (or an extrusion) where theleaking of light through the diffusion membrane is low at the proximalend of the fiber (or light intensity side) and the diffusion cangradually increase as the fiber gets longer towards the distal end ofthe fiber. The outer membrane can be scaled to allow for uniform/evenlight and power deposition along the length of the fiber.

A diffusive membrane can be deposited in specific thicknesses orpatterns on the fiber to achieve uniform delivery of light. In someembodiments, segments of diffusive material can be applied to the outersurface of the fiber in an arrangement that provide uniform light alongthe length thereof. In some embodiments, a diffusive coating (e.g., aspray coat, dip coat, or ionic deposition coating) can be applied to thefiber such that the thickness of the coating decreases along the lengthfrom the proximal end to the distal end of the fiber. The thinning ofthe coating towards the distal end allows for an increase in the amountof light diffusion through the coating from the proximal to the distalend such that the end result is uniform delivery of light along thelength of the fiber. As described herein throughout the disclosure andthe various embodiments, the energy across the length of the fibers (thelinear deposition of even power) is uniform such that the bacteria orother microbe at the treatment site will be killed at an even rate.

Exemplary characteristics of PMMA plastic optical fiber (POF):

-   -   PMMA and polystyrene are used as the core, with refractive        indices of 1.49 and 1.59 respectively.    -   Generally, fiber cladding is made of silicone resin (refractive        index ˜1.46).    -   High refractive index difference is maintained between core and        cladding.    -   High numerical aperture.    -   Have high mechanical flexibility and low cost.    -   Industry-standard (IEC 60793-2-40 A4a.2) step-index fiber has a        core diameter of 1 mm.    -   Attenuation loss is about 1 dB/m @ 650 nm.    -   Bandwidth is ˜5 MHz-km @ 650 nm.

The cladding of POF is a thin, embedded/impregnated layer to maintainthe light within the core. The cladding can be very thin (for example,10 micron) in standard 1 mm step index. A diamond pointer, such as adiamond blade or other “super sharp” edged device can be used to removea small very thin amount of the cladding from the fiber.

The use of multistrand optical fibers all held in contact proximity withthat of a light source, where the termination end of the emitter facesof the fibers are aligned with reflective shapes within the tube tocause the even dispersion of light over the length of the system as eachindividual light fiber is delivering the originating energy amount.

The fibers are of different lengths, and each specific length fiber orfibers terminates on or near the reflective face of the intermediatelight diffusion member

A light-dispersing element with the cladded surface designed to containthe light within the element is modified so as to evenly bleed outlight.

The light-diffusing element can include a surface coating which acts asa scattering surface coating The coating can be comprised of a phosphor,a fluorophore, etc.

The light dispersing element can be coupled to efficiency deliver lightfrom LED sources.

Short segments of light-dispersing elements can be mounted on the faceof LEDs, with multiple segments comprising a chain to thereby constructa length to provide sufficient and even energy deposition.

The light element may be a glass rod that includes a plurality ofinternal voids such that when light is directed through the element thevoids cause the light to be scattered in a transverse direction, exitingthe lateral surface of the element to provide a broad-area illuminationeffect.

The light element can be configured to be a flexible or malleable rod.In some embodiments, the rod can be rigid or it can be bent in a gentlecurve/curves.

The light fiber can be constructed as a two part system having an innerfiber which is merely a plastic fiber conductor (without the traditionalcladding) and an outer layer, a tube, that created intimate contact withthe inner plastic fiber, that functions as a cladding.

The outer layer can be applied to the inner fiber and can have a surfacecoating which acts as a light scattering surface. The means of lightscattering is either a coating of or an infusion of nanoparticles in anextrusion. For example, the coating may be comprised of a phosphor or afluorophore to affect the scattering.

As previously mentioned, the bleeding out of light results in acontinual loss of light intensity, and over the length of the fiber,results in a loss of roughly 90% intensity over a 10 length distance(nonspecific length) hence the proximal end is far more intense thanthat of the distal end. To prevent this imbalance of light, which wouldpreclude the fibers use in either curing or delivery of antimicrobialblue light, a modification to the coating can be used.

In some embodiments, the modification to the coating is that it can bethicker or less transparent to minimize light transmission through thefiber (and decrease loss) at the proximal end of the fiber, as shown inFIG. 18 . The coating or cladding 460 can decrease in thickness from theproximal end to the distal end of the fiber 462, increasing thetransmission at the end of the fiber. For example, it can be assumedthat the amount of light transmission through the cladding is sufficientat the proximal end and can match to the amount of light transmission atthe distal end.

The applied outer layer extrusion has a tapered or variable delivery ofthe nanoparticles, with the proximal end of the coating having a greaterpercentage of non-diffusion particles and more opacity, and with thedistal end of the coating having more diffusion particles and lessopacity. In some embodiments, the nanoparticles have a cross-sectionaldimension of at least 25 nm. The nanoparticles have an averagetransmittance, per mm thickness, over the wavelength range from 400nm-700 nm of greater than 90%.

The light-diffusing optical fiber coating, where the secondary coatinglayer of the extrusion is the outermost coating.

The cladding may be glass or a polymer. Cladding glasses include silicaglass or modified silica glass. Cladding polymers include, but are notlimited to, acrylate polymers, or fluorinated variants thereof(fluoroacrylate polymers).

Delivering Light to Cavities of the Bone

The light can be delivered to the bone using a variety of mechanisms.

In some embodiments, one or more fibers is configured to deliver thelight (the removal of the cladding in the traditional spiral fashion).For small diameter canals, for example metacarpals, metatarsals, shaftof the ulna, the one or more fiber are straight. A passageway is createdinto the bone and the fiber can be fed into position. For largerdiameter canals, the one or more fibers are heat set in a coiledconfiguration similar to the thread on a screw or a bolt, as shown inFIG. 19 . Coiled fibers 470 are delivered into the canal via a sheath472 where the sheath holds the precoiled fiber in a straight linearfashion and the removal of the sheath has the coiled fiber regaining thespiraled/coiled form down the length of the bone. The coiled systemexpands and achieves intimate contact with the endosteal surface.

In some embodiments, a plurality of fibers can be bundled together andused to deliver light along the length of the treatment site such thateach fiber or subsets of the fibers in the bundle are cut to differentlengths. All the fibers in the bundle are illuminated with a singlesource and the light energy delivered by each fibers at its tip areequal, but because the lengths of the fibers vary the light will bedelivered uniformly along the length of the bundle of fibers from theshortest fiber in the bundle to the longest fiber in the bundle.

In some embodiments, it is possible to pulse the light delivered to thetreatment site (tissue and/or bone) with intervals of higher powerdensities or by turning the light source on and off rather than aconstant application of light. This can be useful for disinfecting largeamounts of CFUs, and/or improving the efficiency of the disinfectionprocess, and/or combating aggressive or robust forms of pathogens.Additionally, by adjusting the power density and the exposure time, thetotal energy density delivered to the pathogen sample may be adjusted.By pulsing the power, the correct dose of light can be delivered, orsequential doses of light can be delivered over a period of time. Thiscan be done with systems that can be hardwired or plugged into a powersource, or with a system that utilizes batteries or other portable powersources. The variability of the delivery of power to the system tocontrol the duration and timing of the delivering of time can also beused for long term treatment, for example in a portable or wearableversion such as bandages, or within indwelling catheters (e.g., urinarycatheters), as described herein.

In some embodiments, the exposure time for each pulse of light in a timeinterval may be greater than the off period of time. In someembodiments, the exposure time for each pulse of light is less than theoff period of time. Similarly, while the term “off period of time” isused herein with reference to a period of time where no light is outputto the pathogen sample, one skilled in the art may configure the pulsedlight output by the blue-violet light delivery system (or one or morelight diffusing optical fibers) to have a first power density during afirst exposure time followed by a second power density during a secondexposure time that is different than the first power density.Furthermore, both the first power density and the second power densitymay be greater than 0 mW/cm2.

FIG. 20 illustrates exemplary modes of light source operation that canbe continuous or pulsed. The pulsing characteristics can be defined bythe pulse duration (width), reported in seconds; pulse intervals,reported in seconds; and pulse frequency (number of pulses per second,in Hz). In more sophisticated pulsing sequences, especially in ultrafastpulses (nanoseconds, picoseconds, or femtoseconds), a series of pulsestermed the pulse train are followed by a pulse gap. This is usuallyreported as time (e.g., picoseconds). The duty cycle refers to the timethe beam is on during entire treatment. For a continuous wave, this is100%, although it can vary significantly with pulsing regimens.

The fiber may be delivered within the canal in a variety of ways. Insome embodiments, a hollow cannula is delivered within the canal and thefiber is introduced within the lumen of the cannula. The cannula canthen be removed from the canal, e.g., slid backwards, over the fiber soas to allow the fiber to be exposed within the canal. The cannula can bemetal or plastic, and can be stiff or malleable to allow appropriatedelivery. The strength and stiffness of the cannula dependent upon thearea of the body anatomy requiring the requisite force to delivery it.

The delivery system is capable of irrigation and aspiration of fluids,and the light system can be used in conjunction with an intramedullaryreaming or surgical irrigation aspiration system. The fluids can bewater, H2O2, acetic acid, povidone iodine, one or more essential oils,or a combination of antibiotics (irrigation of low concentration ofH2O2, with concentrations of high does H2O2). The delivery port for thefiber may have an irrigation port at the entrance point to the bone anda longer aspiration point catheter that is further down the length ofthe bone. The irrigation aspiration can be continual during the processto provide a clean canal to ensure that the light fiber is not coveredor occluded with intramedullary materials.

In some embodiments, the use of the light system in conjunction withessential oils, H2O2, acetic acid, and/or povidone iodine providesantimicrobial effect. Essential oils/photosynthesizers can be used toimpregnate or identify the bacteria such that the bacteria becomecharged to allow for more effective blue light treatment. With somebacteria, the blue light can be used to damage the shell of thebacteria, and the essential oils or peroxide then can break down thebacteria further. In some embodiments that include an inflatableballoon, the balloon can include an edge or a lip such that the solution(i.e., an essential oil) can be poured over the balloon to impregnatethe balloon with the solution for treating a specific bacteria.

For example, the association of aminoglycosides with the blue LED lightand essential oils can be used against resistant bacteria.

The essential oils of aegle, ageratum, citronella, eucalyptus, geranium,lemongrass, orange, palmarosa, patchouli and peppermint, were tested forantibacterial activity against 22 bacteria, including Gram-positivecocci and rods and Gram-negative rods, and twelve fungi (3 yeast-likeand 9 filamentous) by the disc diffusion method. Lemongrass, eucalyptus,peppermint and orange oils were effective against all the 22 bacterialstrains. Aegle and palmarosa oils inhibited 21 bacteria; patchouli andageratum oils inhibited 20 bacteria and citronella and geranium oilswere inhibitory to 15 and 12 bacterial strains, respectively. All twelvefungi were inhibited by seven oils (aegle, citronella, geranium,lemongrass, orange, palmarosa and patchouli). Eucalyptus and peppermintoils were effective against eleven fungi. Ageratum oil was inhibitory toonly four fungi tested. The MIC of eucalyptus, lemongrass, palmarosa andpeppermint oils ranged from 0.16 to >20 microliters ml-1 for eighteenbacteria and from 0.25 to 10 microliters ml-1 for twelve fungi.

The coiled system can be left in place for a single dose of light or forlonger periods of time (i.e., for multiple days) to achieve multipledoses of light. The entry point of the light fiber into the canal is amedical grade antibiotic covering to preclude incremental bacteria orthe transmission of materials into the canal. The irrigation aspirationcatheter can be left in place during the illumination and can be removedpost the illumination where the irrigation port may allow the infusionof antibiotics. The system may be left in place for a period of days sothat multiple activations of light can be applied, and the irrigationport can be used to provide continual drip/or small dose of antibioticswithin the canal of the bone.

The external aspect of the fibers (those outside of the anatomy) arecontained within a supportive sheath so as to protect them, for exampleto prevent accidental breakage. The delivery port for the light fiberfor the indwelling catheter is sealed to the external environment aroundthe light fiber, for example using a port. The sealed port allows forthe ability to deliver intramedullary antibiotics or intramedullaryfluids.

Multiple fibers delivered within the canal can be held in intimatecontact to each other, for example, via clear bands, retaining clips, orother mechanism, or they can be delivered and released from the intimatecontact to the other fibers.

Multiple fibers can be powered by multiple LEDs or a single LED. Powercan be adjusted via the amount of time that the system is run. Thesystem can be used to aspirate fluids from the canal. The system can beused to acquire intramedullary samples from the canal.

Fibers on outside of the balloon can be held in retaining tubes/columnsor lumens on the outside of the balloon. The inside of the balloon orthe outside of the balloon can be comprised of a reflective surface toenhance the light as extraneous light will be reflected to the endostealsurface.

Devices for Delivering Fibers for Treating Larger Areas

For surface treatment of wounds or use in conjunction with proceduresthat require larger area coverage of the ABL light, the light fibers canbe built to create a larger structure such as a paddle 480, as shown inFIG. 21 . The shape of the paddle can vary and can include a plate-shapeas shown in FIG. 21 , but it will be understood that the paddle can takeany shape required based on the size of the area to be treatment and thesize and shape of the area of the body into which the paddle isinserted. In some embodiments, the paddle holds a single fiber coiled.In some embodiments, the paddle holds multiple fibers coiled. The fiberscontained within a paddle can be rigid or semi rigid so as to bemalleable to take shapes as required.

The paddle can have one side that is optically clear and one portionthat is opaque so that the light only emanates from the paddle in onegeneral direction outwards. The size of the optically clear portion maybe predefined. There may be a covering on the paddle that allows foradjustment of the open area that can be slidable, hinged, pivotable, orother means to cover and occlude the light from being transmittedoutwards. The inner surface of the paddle on the opaque side can be apolished reflective surface that reflects and focuses the light from theone or more fibers outward.

The shape of the paddle surface can be that of an optical reflector soas to gain as much of the light from the rear of the fiber to bedelivered outwards. These reflective shapes may follow the shape of thefibers that have been laid within the paddle such that each of the fibersits within a curved reflective recess within the paddle. Thesereflective shapes may follow the shape of the fibers that have beencoiled such that each of the fiber sits within a curved reflectiverecess within the paddle. A paddle can be a square, rectangle orcircular form. The paddle variants therein can be used to deliver lightduring a surgical procedure where the wand is delivered within thesurgical cavity to provide continual light to the affected tissues.

In some embodiments, the paddle (or any of the other shapes describedherein) can be constructed to be malleable such that the paddle, wand,or other shape can be bent, shaped, and/or formed so it can beintroduced within a cavity during an open procedure. For example, it canbe affixed to a retractor or other instrumentation so that the lightsource is directed within an incision, or it can be shaped or bent asrequired to be placed within a bodily orifice.

Devices for Delivering Fibers to Confined Areas

In some embodiments, a device can include a series of shorter lengthfibers 2-4 inches, or 3-5 inches, running in parallel (like a fork or acomb), as shown in FIG. 22A and FIG. 22B. FIG. 22A illustrates a topview of an embodiment of optical fibers 492 running parallel for form acomb-like structure 490. As shown in the cross-sectional view in FIG.22B, each fiber run parallel and is positioned in a rounded opening thatforms a focal reflector. In some embodiments, the fibers reside withinfocal reflectors, with one side being opaque and one side forillumination. The curved reflective shape directs the light that is notin the direction of the intended use and reflects and focuses itoutwards.

FIG. 23A represents the position of the fiber relative to the rearreflector (or reflective surface) 494. FIG. 23B illustrates the fiber492 within the rear reflector, and showing the ability to adjust theopening exposure of the illumination area or close it completely usingslidable shields 494 to block or focus the beam. For example, thereflector can include one or more gates to control and focus the amountof light affecting tissue.

Catheter with Wand Configuration for Delivering Fibers

The surface treatment of wounds or the use in conjunction withprocedures that require larger area coverage of the ABL light can beachieved by creating a wand 500 from the light fibers 502, as shown inFIG. 24 . The wand can hold a single fiber or multiple fibers. Thefibers can be contained within a rod or tube. The wand can be in theform of a plate or other shape as needed and can be rigid or semi rigidso as to be malleable to take shapes as required. The rod/tube can haveone portion that is optically clear and one portion that is opaque sothat the light only emanates from the wand in one general directionoutwards. The optically clear portion can vary in size, and for examplemay be 30 degrees, 45 degrees, 60 degrees, or 90 degrees. The opticallyclear portion may be predefined. There may be a covering on the wandthat allows for adjustment of the open area, from a maximum of 90degrees down to 15 degrees. The inner surface of the wand on the opaqueside of the tube can be a polished reflective surface that reflects andfocuses the light from the fiber/fibers outward. The shape of thewand/reflective surface can be that of an optical reflector so as togain as much of the light from the rear of the fiber to be deliveredoutwards.

In some embodiments, the fibers can be placed within a large bore needlethat includes areas where the sides of the needle are removed so as topermit illumination outwards. The bore needle allows the flexible fiberto be inserted/introduced into a depth of tissue so as to illuminate anarea that is not exposed. In the case of a mass, such as a tumor orother defined area that needs to be illuminated, the bore needle allowsthe introduction of the fiber to be delivered to points and locationswhere the flexible fiber does not permit insertion. The cut away of theneedle provides illumination such that the bore of the needle can bewithdrawn while leaving the fiber within the body. The bore needle canpermit access to areas where the fiber alone might not be able to bedelivered but access needs to be made in a minimally invasive fashion.

Catheter with an Inflatable Member

According to aspects of the disclosed subject matter, a method forproviding an anti-microbial effect on a bone comprises gaining access toa cavity in a bone; delivering in an unexpanded state, an expandablemember having at least one channel to the cavity in the bone; infusingthe at least one light sensitive liquid in the expandable member to movethe expandable member from a deflated state to an inflated state,positioning an optical fiber sufficiently designed to emit light energyalong a length of the optical fiber inside the at least one channel inthe expandable member; activating a light source engaging the opticalfiber; and delivering light energy from the light source to the opticalfiber to providing an anti-microbial effect on a bone

In some embodiments, an inflatable member, such as a balloon, can bedelivered in an uninflated fashion. The balloon can be inflated using avariety of substances, including air or water, to expand the balloonagainst the endosteal surface of the bone. A light source can beactivated, and the energy delivered to the bone and/or bacteria. Asshown in FIG. 25A, if a balloon 510 is utilized, in some embodiments thefibers 512 are located outside of the balloon such that when the balloonis inflated, it expands and distends the balloon shape so that thefibers are pushed outwards. FIG. 25B illustrates a top view of thefibers 512 located circumferentially on the outside of the balloon 510.This allows for the fibers to be direct or close contact with theendosteal surface (inside of the bone wall). The intimate or closecontact can increase the effective power of the light as it is closer tothe wall (less loss of power via distance). In some embodiments, theouter surface of the balloon and/or the interior of the balloon can bemirrored or include a reflective portion so as to enhance the deliveryof light from the fibers.

In some embodiments, utilization of a balloon can act to increasespatial volume and reduce fluid volume. A reduction in the treatedvolume can result in an increase in the energy deposition, and that theincrease in volume can result in more of the fiber transmitting light tothe fluid. The use of a balloon reduces the illumination energy (inversesquare law). In some embodiments, the power per volume, due to theballoon displacement and lower sample volume, exceeds the losses due toillumination distance.

Two issues are at play here: power and volume. Distance as it relates topower can also be a factor. For example, if the energy is 500 units(undefined) and the volume of solution to be treated is 3000(undefined), then the energy delivered per volume is 3000/500=6 volumeunits per 1 energy unit. The effective power per volume is ⅙. If thevolume is reduced to 1000 with the same energy level, the effectivepower per volume is ½. A reduced volume of solution can provide morepower per volume and more effective elimination of bacteria.

As one moves further away from the light source, the intensitydecreases. Thus, the ability to increase the power can be to reduce thevolume of solution in the balloon (where the volume per unit of energyis greater than the loss of intensity by distance). In some embodiments,the choice of balloon to achieve the reduction may be important. Forexample, a longer thinner balloon to achieve the reduction may be betterthan a larger diameter, where the volume is decreased but the distanceto the source is so far that the intensity of the light has decreased.

The reason that the fibers in the balloon, or the fibers on the outsideof the balloon, or the wand of light are important to the process isthat they cause a reduction in the internal space of the materialswithin the canal, decreasing the distance that the light needs to travelto accomplish antimicrobial effect. Allowing for the fibers on theoutside of the balloon achieves a decrease in the distance between thetissue and/or bone and the light for treatment.

Conversely, with the fibers on the outside of the balloon, the distanceto the edges of the bone is reduced (for example, an 18 mm balloon and a2 mm distance for the light to travel). Thus, as the balloon expands,the fibers on the outside of the balloon are pushed closer to the tissueand/or bone, which also decreases the distance between the fibers andthe treatment site to achieve greater light illumination without havingto increase the power. The fibers can be positioned on the outside ofthe balloon such that the fibers are moved towards the treatment sitewhen the balloon is expanded.

In some embodiments, the number of fibers can be decreased if the fiberscan be moved closer to the target site. This increases the intensity ofthe light from each fibers, resulting in the use of less fibers, butwith the resulting intensity remaining substantially the same. Thevariables include power (driven power), distance which determinesintensity, time (as time defines joules), and the number of fibers (morefiber decreases distance), and lateral distance between the nextsequential fiber (thereby requiring each fiber to cover less area).Hence the fibers being in closer proximity to the bone makes the systemsignificantly more efficient, but a light source of 2200 would have tobe used to achieve the same effect as the 2 mm distance. The inversesquare law applies when looking at the light source versus distance suchthat as the light source gets further away, the intensity decreases.

Of concern to the either high power or long duration run of the systemwhere the joules are significant is the fact that interim located tissuemay be impacted by the illumination at these lengths and powers.

In some embodiments, a light source can be positioned inside a lightdiffusion balloon that is used as the light delivery device. The ballooncan have a nano surface to spread the internally reflected light. Thelight source can be powerful enough to provide the power in milliwattsto achieve the required joules at full expansion of the balloon. Thelight source can be comprised of a multistrand fiber (end fiberillumination) cut at increased length sections, with the segmentedlengths of the illumination fiber providing even outward illumination.The light fiber can be a diffusion surface on a solid glass, sapphire,or other transmissive material. The light transmission system can havemultiple reflective members to increase the transmission area of thelight. The light is dispersed to the surrounding tissues/bone by thereflective members of the central light fiber. While the intensity ofthe energy delivered within the balloon may be “even,” the diffusionsurface ensures the even power distribution. The diffusion surfacereduces the need for the precise power distribution of the light fiber.The internal surface of the balloon is reflective such that nonattenuated light is reflected back into the balloon where it amplifiesthe energy. The surface can be a part of the balloon or an appliedsurface thereafter.

In some embodiments, a balloon with two walls can be used, such that thespace between a first wall and a second wall contains one or more fibersthat can be wrapped circumferentially around the balloon. The lightfibers around the circumference can be positioned to deliver light, andfibers that are wrapped around the balloon are emitters, cut atdifferent lengths so as to achieve the same amount of optical power ateach cut surrounding length. The active portions of each segment are thesame so via a multifilament stacking there can be equal opticalintensity.

In some embodiments, the diffusing balloon catheter is a softcylindrical balloon catheter with translucent diffusing walls. Used withan internal radial light diffuser, the diffusing balloon catheter,provides a homogeneous illumination of biological tissues in contactwith the balloon walls. The compliant property of the balloon in contactwith the walls of the bone or tissue, allows the balloon to adapt itsshape to the geometry and consequently to provide an accurate dosimetryof light to the affected area. The balloon can be inflated with water tominimize refraction and adapts its shape to the internal diameter of thebone canal, or the balloon can be inflated with air or any othermaterial capable of inflating the balloon and allowing the light todiffuse.

In some embodiments, there is a fitting at the base of the balloon tipthat holds the fibers in position such that the side of the fiberwithout the cladding is held in position and emits light outward. Thefull cladded side is against the balloon. FIG. 25C illustrates anembodiment of the removed cladding on the fiber. There is a fitting atthe catheter/top of the balloon where the fibers are located andconstrained that they are in vertical alignment up the balloon so thatthe base of the fiber and the tip of the fiber are in alignment. In someembodiments, the constraining member is at the top of the balloonresiding on the catheter. This allows the fibers to slide through theconstraining member as the balloon is expanding and pulling the fibers.In some embodiments, as shown, the cladding to partially removed fromthe fiber but is not fully spiraled.

Referring to FIG. 1A, FIG. 1B, FIG. 1C and FIG. 2A and FIG. 2B, for thesystem to deliver the light to the cavity of the bone, the system 100further includes a balloon catheter 110 having an elongated shaft 101with a proximal end 102, a distal end 104, and a longitudinal axis therebetween. In an embodiment, the balloon catheter 110 can have an outsidediameter ranging from about 3 mm (9 French) to about 8 mm (24 French).In larger diameter canals, for example, the femur or tibia, the OD ofthe balloon when inflated can be various sizes, including 22 mm.However, it is noted the balloon catheter 110 may have an outsidediameter of about 3 mm (9 French). At least one inner lumen isincorporated within the elongated shaft 101 of the balloon catheter 110.The elongated shaft 101 of the balloon catheter 110 may include twoinner lumens. The elongated shaft 101 of the balloon catheter 110 mayinclude three inner lumens, four inner lumens or more. It iscontemplated the one or more inner lumens may accept one or more opticalfibers. The proximal end 102 of the balloon catheter 110 includes anadapter for passage of at least one of inflation fluids or medicalinstruments.

The distal end 104 of the balloon catheter 110 includes at least oneexpandable member 170. The expandable member 170 of FIG. 1A has abulbous shape; however, the expandable member 170 may have any othersuitable shape. It is possible, the at least one expandable member 170includes multiple expandable members. For example, the distal end 104 ofthe balloon catheter 110 may include a first inner inflatable balloonpositioned inside and completely surrounded by an outer inflatableballoon. In an embodiment, the expandable member 170 can be manufacturedfrom a non-compliant (non-stretch/non-expansion) conformable material.In an embodiment, the expandable member 170 is manufactured from aconformable compliant material that is limited in dimensional change byembedded fibers. One or more radiopaque markers, bands or beads may beplaced at various locations along the expandable member 170 and/or theballoon catheter 110 so that components of the system 100 may be viewedusing fluoroscopy.

FIG. 1B and FIG. 1C show schematic illustrations of embodiments of abone implant device. The devices include a balloon catheter 110 and anexpandable member 170 sufficiently shaped to fit within a space, cavityor a gap in a fractured bone. It is contemplated the expandable membermay be of any shape so as to fit within a space, cavity or a gap in afractured bone. For example, the expandable members 170 of FIG. 1B andFIG. 1C can have a tapered elongated shape to fill the space, cavity orgap in certain fractured or weakened bones to be repaired or stabilized.In an embodiment, the expandable member 170 can have an antegrade shapeas shown in FIG. 1B. In an embodiment, the expandable member 170 canhave a retrograde shape as shown in FIG. 1C. In FIG. 1B, the expandablemember 170 can have a larger diameter at its distal end than theproximal end. In FIG. 1C, the expandable member 170 can have a largerdiameter at its proximal end than the distal end.

In the embodiments shown in FIG. 1A, FIG. 1B, and FIG. 1C, the proximalend of the balloon catheter 110 includes a first port 162 and a secondport 164. The first port 162 can accept, for example, thelight-conducting fiber 140 or multiple light-conducting fibers. Thesecond port 164 can accept, for example, a syringe 160 housing alight-sensitive liquid 165. In an embodiment, the syringe 160 maintainsa low pressure during the infusion and aspiration of the light-sensitiveliquid 165. In some embodiments, the syringe 160 maintains a lowpressure of about 10 atmospheres or less during the infusion andaspiration of the light-sensitive liquid 165. In some embodiments, thesyringe 160 maintains a low pressure of less than about 5 atmospheresduring the infusion and aspiration of the light-sensitive liquid 165. Insome embodiments, the syringe 160 maintains a low pressure of about 4atmospheres or less during the infusion and aspiration of thelight-sensitive liquid 165. In some embodiments, the light-sensitiveliquid 165 is a photodynamic (light-curable) monomer. In someembodiments, the photodynamic (light-curable) monomer is exposed to anappropriate frequency of light and intensity to cure the monomer insidethe expandable member 170 and form a rigid structure.

Thus, the method may optionally include curing a light-curable fluid,such as a monomer, inside the balloon to harden the expandable member.In some embodiments, an optical fiber can be positioned inside theexpandable member and the light source can be activated to deliver lightenergy to the optical fiber from the light source to cure the expandablemember using the at least one light sensitive liquid that has beeninfused into the expandable member after light from the fibers has beenused for an antimicrobial treatment.

FIG. 2A and FIG. 2B show close-up cross-sectional views of the regioncircled in FIG. 1 . FIG. 2A shows a cross-sectional view of a distal endof the balloon catheter 110 and the expandable member 170 prior to thedevice being infused with light-sensitive liquid. FIG. 2B shows across-sectional view of the distal end of the balloon catheter 110 andthe expandable member 170 after the device has been infused withlight-sensitive liquid and light energy from the light-conducting fiberis introduced into the balloon catheter 110 and inner lumen of theexpandable member 170 to cure the light-sensitive liquid.

As illustrated in FIG. 2A and FIG. 2B, the flexible balloon catheter 110includes an inner void 152 for passage of the light-sensitive liquid165, and an inner lumen 154 for passage of the light-conducting fiber140. In the embodiment illustrated in FIG. 2A and FIG. 2B, the innerlumen 154 and the inner void 152 are concentric to one another. Thelight-sensitive liquid 165 has a low viscosity or low resistance toflow, to facilitate the delivery of the light-sensitive liquid 165through the inner void 152. In an embodiment, the light-sensitive liquid165 has a viscosity of about 1000 cP or less. In an embodiment, thelight-sensitive liquid 165 has a viscosity ranging from about 650 cP toabout 450 cP. The expandable member 170 may be inflated, trial fit andadjusted as many times as a user wants with the light-sensitive liquid165, up until the light source 110 is activated, when the polymerizationprocess is initiated. Because the light-sensitive liquid 165 has aliquid consistency and is viscous, the light-sensitive liquid 165 may bedelivered using low pressure delivery and high pressure delivery is notrequired, but may be used.

In some embodiments, the expandable member can be trial fit into a spacewithin a bone by alternatingly moving between a deflated state and aninflated state by a fluid, such as water, air, or a light sensitiveliquid. The expandable member is designed to be at least partiallyplaced into the space within the bone, and directly in contact with thebone and to form fit to a surface contact area within the space of thebone. A light conducting fiber sized to pass through the inner lumen ofthe delivery catheter and into the expandable member to disperse lightenergy to provide an anti-microbial effect. In some embodiments,subsequently a light sensitive liquid can be infused into the expandablemember, and the light conducting fiber can be positioned in theexpandable member to initiate hardening of the light sensitive liquidwithin the expandable member to form a photodynamic implant of a sizeand a shape so the bone is restructured to a substantially original sizeand an original shape around the formed photodynamic implant.

FIG. 2C and FIG. 2D show a close-up cross-sectional view of the regioncircled in FIG. 1B and FIG. 1C, respectively. FIG. 2C and FIG. 2D showcross-sectional views of a distal end of the balloon catheter 110 andthe expandable member 170 and a light-conducting fiber 140 with a cut141 in the fiber in the balloon catheter 110 and inner lumen of theexpandable member 170. The device also has a separation area 172 at thejunction of the balloon catheter 110 and the expandable member 170 wherethe balloon catheter 110 may be separated from the expandable member170.

Channels within the Expandable Member for the Optical Fibers

FIG. 26 shows a view of another embodiment of a distal end of a ballooncatheter of the present disclosure. The distal end of the ballooncatheter includes expandable member 170, which comprises an inflatableballoon 301. The inflatable balloon 301 has a wall with an outer surface305 and an inner surface 330. The inner surface 330 defines an innercavity 335.

Further, at least one channel 303A is located in the cavity 305 of theinflatable balloon 301 approximate the inner surface 330 of theinflatable balloon 301. The balloon catheter includes an elongated shafthaving a first inner lumen 311 in fluid communication with theexpandable balloon 301 which is also in communication with the at leastone channel 303A. A separate optical fiber 306 can be incorporatedwithin the elongated shaft of the balloon catheter and encircle theinner surface of the expandable balloon 303A within the at least onechannel 303A.

Further, the elongated shaft of the balloon catheter includes a secondinner lumen 313 in fluid communication with the expandable balloon 301,wherein another channel (not shown) or multiple channels (not shown) maybe incorporated. For example, the additional channels may be used foradditional optical fibers that can be incorporated within the elongatedshaft of the balloon catheter and encircle the inner surface(s) of theexpandable balloon 303A. It is possible that, the channel or channelsmay be shaped longitudinally within the expandable member, wherein theremay be 1, 2, 3, 5, 8 or more longitudinal channels extending from oneend to another end of the expandable member. It is possible that alongitudinal channel or channels may be inter-connected with one or moreother channels, so that an optical fiber or multiple optical fibers mayextend there through. The longitudinal channel may be linear, non-linearor some combination thereof extending from one end to another end of theexpandable member.

In some embodiments, the channel or channels may be spiral shaped withinthe expandable member, wherein there may be 1, 2, 3, 5, 8 or more spiralchannels. It is possible that a spiral shaped channel or channels may beinter-connected with one or more other channels, so that an opticalfiber or multiple optical fibers may extend there through. The spiralshaped channel or channels may be linear, non-linear or some combinationthereof. At least one aspect, by non-limiting example, among otherthings, is that the channel or channels can be configured to provide amaximum amount of light to the bone walls within the cavity of the bone.At least one benefit, among other things, of a spiral configuration isthe large amount of light provided.

Ridges located on an outer surface of expandable member having at leastone channel for the Optical Fibers

FIG. 27 shows ridges 309 located on an outer surface 305 of the balloon301 of the expandable member 170, wherein the ridges 309 include atleast one channel 303B for the optical fibers 306 to enter therethrough. The distal end of the balloon catheter includes expandablemember 170, with the inflatable balloon 301 includes an inner lumen 311and one or more ridge 309 located the outer surface 305 of theinflatable balloon 301, wherein at least one or more channel 303B islocated within the one or more ridge 309. The ridge 309 can beconfigured to incorporate at least one or more channel 303B for at leastone or more optical fiber 306, such that the at least one or moreoptical fiber 306 is capable of entering and exiting the at least one ormore channel 303B.

The ridge or ridges 309 may be shaped longitudinally along an outersurface of the expandable member, wherein there may be 1, 2, 3, 5, 8 ormore longitudinal ridges 309 extending from one end to another end ofthe expandable member 170. It is possible that a longitudinal ridges 309may be inter-connected with other ridges 309, so that an optical fiberor multiple optical fibers 306, i.e. within the channel's 303B of theridges 309, may extend there through. The longitudinal ridges 309 may belinear, non-linear or some combination thereof extending from one end toanother end of the expandable member.

The ridges or channels that are described could also be the means forthe delivery of the irrigation fluids (for example, the H2O2). They alsocould be set in a series. For example, the even numbers of them (i.e.,2, 4, 6, 8) are the irrigation versions, and the weep holes for thefluid is at the proximal aspect, where the aspiration channels are theodd numbers channels (i.e., 1, 3, 5, 7) have small holes at the distalsection of the channel to pull the materials out of the canal, therebyhaving the irrigation aspiration on the circumference.

In some embodiments, the ridge or ridges 309 may be spiral shaped withinthe expandable member 170, wherein there may be 1, 2, 3, 5, 8 or morespiral ridge or ridges 309. It is possible that a spiral shaped ridge orridges 309 may be inter-connected with one or more other channels, sothat an optical fiber or multiple optical fibers 306 may extend therethrough. The spiral shaped ridge or ridges 309 may be linear, non-linearor some combination thereof. At least one aspect, by non-limitingexample, among other things, is that the ridge or ridges 309 can beconfigured to provide a maximum amount of light to the bone walls withinthe cavity of the bone.

The ridges that include channels are configured to provide access forpassing optic fibers to pass there through and within the cavity of thebone; either prior to, during the delivery of the light-sensitiveliquid, or after the light-sensitive liquid has been cured and hardened.It is contemplated the optical fiber(s) may provide for an antimicrobialeffect while light-sensitive liquid is infused through the inner void210 in the delivery catheter 101 and enters the inner cavity 295 of theexpandable member 170.

Channels Having One or More Reflective Prisms, i.e. MagnificationDevices, for Magnifying Light from the Optical Fibers

FIG. 28 is similar to and includes the elements of FIG. 26 , however,FIG. 28 shows a channel or channels 303A configured with at least one ormore reflective prisms 317, i.e. magnification devices, for magnifyinglight from the optical fibers. The reflective prisms may includereflective prism arrays, reflective prism assemblies and the like,wherein the reflective prisms can be located along the channels 303A,303B, and/or at an end of the channels 303A, 303B. The reflective prismcan be used to reflect light, in order to flip, invert, rotate, deviateor displace the light beam from the optical fiber. For example, thereflective prism may comprise of different types of materials, includingreflective tape, among other things.

Ribs Having One or More Reflective Prisms, i.e. Magnification Devices,for Magnifying Light from the Optical Fibers

FIG. 29 is similar to and includes the elements of FIG. 27 , however,FIG. 29 shows a ridge or ridges 309 configured to include at least oneor more reflective prisms 318, i.e. magnification devices. Thereflective prisms may include reflective prism arrays, reflective prismassemblies and the like, wherein the reflective prisms can be locatedalong the ridge or ridges 309, and/or at an end of the ridge or ridges309. The reflective prism can be used to reflect light, in order toflip, invert, rotate, deviate or displace the light beam from theoptical fiber.

Manifold Incorporated within an End of Expandable Member for AllowingAccess to Channels for the Optical Fibers

FIG. 30A and FIG. 30B show at least one manifold 344, 346 located withinat least one lumen of the expandable member 170.

FIG. 30A is similar to and includes the elements of FIG. 2C, however,FIG. 30A shows the manifold 344 in communication with the at least onelumen of the expandable member 170 and in communication with the one ormore channels (not shown) located within the expandable member 170 asshown in FIG. 26 . The manifold 344, by non-limiting example, canprovide access for one or more light-conducting fiber 306 to enter theat least one lumen of the expandable 170 and through the manifold 344and further into the channels located within the expandable member 170.The manifold 344 is configured to provide access for passing opticfibers 306 within the cavity of the bone; either prior to, during thedelivery of the light-sensitive liquid, or after the light-sensitiveliquid has been cured and hardened.

Still referring to FIG. 30A shows the manifold 344 located at a proximalend of the expandable member 170. For example, the manifold 344 may belocated within a lumen of the expandable member 170 from about an end ofthe separation area 172 closest to the proximal end of the expandablemember 170 to the proximal end of the expandable member 170 (see FIG. 2Cand FIG. 2D). The manifold 344 of FIG. 30A may be utilized by firstaccessing the flexible balloon catheter first port with thelight-conducting fiber (see FIG. 1A, FIG. 1B, and FIG. 1C), then passingthe light-conducting fiber through the inner lumen (see FIG. 2A and FIG.2B), through the a distal end of the balloon catheter and into theseparation area 172 (see FIG. 2C and FIG. 2D), then into at least onelumen of the expandable member to enter into the manifold 344.

FIG. 30B shows a manifold 346 located in a lumen at a proximal area 212of the expandable member 170. Wherein, the manifold 346 of FIG. 30B maybe utilized by entry through the flexible balloon catheter, however, themanifold 346 may be utilized by the optical fiber entering the distalend 214 of the expandable member 170.

Regarding FIG. 30A and FIG. 30B, the manifold 344, 346 may comprise of aflexible material, a non-flexible material or some combination thereof.The manifold 344, 346 may comprise of two or more openings that connectwith two or more channels located within the expandable member.

Removable Cap to Seal Lumens of Expandable Member

FIG. 31A, FIG. 31B and FIG. 31C show views of a distal end of a devicehaving a removable cap for repairing a weakened or fractured bone of thepresent disclosure.

It is contemplated the removable cap may be used after the lightsensitive liquid has been cured, wherein the hardened expandable memberis formed into a formed photodynamic implant. For example, it ispossible the formed photodynamic implant may have a removable cap thatseals the lumen from fluids and/or other tissue from entering, thuskeeping the lumen clean, as well as the light intensity in the future isnot diminished. It is possible the central lumen may include areceptacle for at least one rod that may be used to fill the lumen, suchthat screws on the end of the implant may be designed and/or intended tokeep the lumen clean and optically transparent. Further, lumen can beaccessed in the future by a removal of the cap, and the rod or the capmay have a valve or access point to allow a minimally invasive means topost operatively introduce the light source. Further still, the cap mayhave a valve and/or access port that can be accessed in a minimallyinvasive fashion. It is possible that a small percutaneous needle may beused, where the fiber is introduced through the cap, and/or the fibermay lead in to it. The cap and implant end can be designed to guide andsteer the fiber into the lumen. It is possible that there may be aconical end that acts as a recipient. Further, the cap can be of aradiopaque material that it can be located by x-ray.

FIG. 31A is a view of an embodiment of a distal end 114 of the flexibledelivery catheter 101. The distal end 114 includes the expandable member170 releasably mounted on the flexible delivery catheter 101. Theexpandable member 170 has a wall 202 with an outer surface 205 and aninner surface 230. The inner surface 230 defines an inner cavity 235. Insome embodiments, the delivery catheter 101 may include multiple innerlumens or voids. For example, as shown in FIG. 31A, the deliverycatheter 101 may include an outer tube 209 and a central tube 220concentrically disposed within the delivery catheter 101. An inner void210 may be formed between the outer tube 209 and the central tube 220.The inner void 210 may be utilized for passing a light-sensitive liquidinto the inner cavity 235 of the expandable member 170. In someembodiments, the central tube 220 includes an inner lumen 211 forpassing a light-conducting fiber (which is not illustrated in FIG. 2 )into the expandable member 170 to cure the light sensitive liquid insidethe inner cavity 235 of the expandable member, as described in detailbelow. It should be noted that while the delivery catheter 101 isdescribed as having the central lumen 220 concentric with the outer tube209, the central lumen 220 may be off-set relative to the outer tube209.

The expandable member 170 includes a proximal area 212 and a distal area214. The proximal area 212 of the expandable member 170 is releasablyconnected to the delivery catheter 101. The distal area 214 may beconnected to the delivery catheter 101 in a variety of ways.

In reference to FIG. 31B, in some embodiments, the distal area 214 ofthe expandable member 170 may be connected to a distal cap 300. Thedistal cap 300 terminates and seals off the area 214 (or lumen) of theexpandable member 170 to prevent the flow of a light-sensitive liquidoutside the balloon and the ingress of bodily fluids inside the balloon.One potential benefit of utilizing the distal cap 300 is ease ofmanufacture and more consistent tip quality when compared to traditionalmelt forming of expandable member 170 directly to the delivery catheter.An additional benefit of the use of the distal cap 300 may also includethe ability to reflect back or scatter light radiating from the end ofthe conducting fiber to improve the light-sensitive liquid cure times ordepth of cure. The reflected light from the distal cap 300 may increasethe energy that is directed towards the light-sensitive liquid in theexpandable member 170 and thus may increase the photo-initiation rate(and thus polymerization rate) of the light-sensitive liquid.

In some embodiments, the distal cap 300 may be formed, molded ormachined from an implant grade polymer (e.g., PET), or anotherbiocompatible material. The distal cap 300 may also be made from afilled material. For example, the PET polymer may be blended with aradiopaque material (e.g., barium sulfate, tungsten, tantalum, etc.)such that the distal cap 300 may be viewed with the assistance offluoroscopic imaging. In some embodiments, the distal cap 300 may alsobe covered with a reflective material such as a gold film (or othermetallic highly polished implant grade film) to enable the distal cap300 to reflect light radiating from the end of the light pipe back intothe balloon. This reflected light can help to reduce the cure time ofthe light sensitive liquid contained within the expandable member 170 todue to the increase in light energy directed at the light sensitiveliquid. In some embodiments, the distal cap 300 may also be fabricatedfrom a crystalline material (such as crystalline PET) to block thetransmission of light through the end of the device 100 and to reflectand/or scatter the light back to the light sensitive liquid in theexpandable member 170.

As illustrated in FIG. 31B, a distal cap 300 includes a body 302 havinga proximal end 304 and a distal end 321. The body 302 defines an innercompartment 303 wherein at least one manifold (not shown) may optionallybe positioned. The distal cap 300 may stabilize the at least onemanifold and may minimize movement of the at least one manifold duringthe operation. It is possible the at least one manifold may be securedinside the compartment 303 by press fitting the at least one manifoldinto the compartment 303; applying permanent adhesive on the surfacesbetween the at least one manifold and the compartment 303; melt bondingthe two surfaces together or other techniques.

FIG. 31B and FIG. 31C show the distal end 321 of the body 302 may beeither open or closed. In some embodiments, the distal cap 300 closesthe distal tip 321 of the body 302 to close the distal tip 321. Thedistal cap 300 includes an inner surface 309, which faces the body 302,and an outer surface 310, which faces away from the body 302. In someembodiments, the outer surface 310 of the distal cap 300 may be roundedor smooth to provide the device 100 with an atraumatic distal point. Insome embodiments, the distal cap 300 may have a semi-circular shape witha flat inner surface and a curved outer surface.

In reference to FIG. 31B, in some embodiments, the material forming theexpandable member 170 may be attached to the outer surface of the body302. In some embodiments, the outer surface of the body 302 includesrecessed attachment sections 312 a, 312 b to which the material of theexpandable member 170 can be attached. In some embodiments, the outersurface of the body 302 may be recessed by a depth approximately equalto the thickness of the expandable member material. In this manner, whenthe expandable member material is attached to the body 302, the outsideof the expandable member material is substantially aligned with theouter surface 310 of the distal cap 300. The material of the expandablemember 170 can be attached to the body 302 by a variety of methods,including, without limitation, adhesives such as cyano-acrylates orepoxies, crimping metallic rings over the expandable portion, meltbonding the expandable member to the body 302 with the use of heat(e.g., RF generated), ultrasonically welding the expandable member tothe body 302, or another method or combination of methods.

In reference to FIG. 31C, in some embodiments, the material of theexpandable member 170 may be attached to the inner surface of the body302 of the distal cap 300.

Optic Fibers

The light conducting fibers or optical fibers may include a singleoptical fiber or a plurality of light conducting fibers 140, wherein theoptical fibers may be positioned side-by-side or in parallel in theexpandable member 170 (see FIG. 1B and FIG. 1C). In some embodiments, aplurality of light conducting fibers 140 can be positioned serially withends of adjacent light conducting fibers 140 aligned or abutting onanother in an end to end fashion (see FIG. 1B and FIG. 1C). For example,one light conducting fiber may be positioned in the distal portion ofthe expandable member and another light conducting fiber may bepositioned in the proximal portion of the expandable member 170. In someembodiments, a plurality of light conducting fibers can be positioned ina combination of parallel and serial positions, such as partiallyoverlapping or any other suitable configuration. In some embodiments, aplurality of light conducting fibers can be attached to a single lightsource with a splitter, or can be attached to a plurality of lightsources.

The most basic function of a fiber is to guide light, i.e., to keeplight concentrated over longer propagation distances despite the naturaltendency of light beams to diverge, and possibly even under conditionsof strong bending. In the simple case of a step-index fiber, thisguidance is achieved by creating a region with increased refractiveindex around the fiber axis, called the fiber core, which is surroundedby the cladding. The cladding may be protected with a polymer coating.Light is kept in the “core” of the light-conducting fiber by totalinternal reflection. Cladding keeps light traveling down the length ofthe fiber to a destination. In some instances, it is desirable toconduct electromagnetic waves along a single guide and extract lightalong a given length of the guide's distal end rather than only at theguide's terminating face.

In some embodiments, an optical fiber of the present disclosure ismanufactured from a Lumenyte STA-FLEX® “SEL” END LIGHT OPTICAL FIBER,available from Lumenyte International Corporation of Foothill Ranch, CA,can be employed. These optical fibers may each consist of a lighttransmitting solid large core, a Teflon® clad and a black bondable outerjacket. The optical fiber may transmit light from a light source to thedistal tip for use as a point source. The optical fiber may have a wide80 degree acceptance angle and 80 degree beam spread, allowing the lightto be viewed from more oblique angles. The light transmitting core maybe solid, may have no light diminishing packing fraction losses and maybe easily spliced. The jacket may be bondable. Custom jackets may beavailable for more flexibility and color options. The optical fiber caneach have a transmission loss (attenuation) of less than approximately1.5% per foot, a bend radius (minimum) of approximately 6 times thefiber's diameter, temperature stability of up to approximately 90° C.(194° F.), spectral transmission range of approximately 350-800 nm, anacceptance angle of approximately 80°, a refractive index core ofapproximately 1.48 or greater, cladding of approximately 1.34 or lessand a numerical aperture of approximately 0.63. The length of theoptical fiber can be approximately 100 continuous feet. Splicing may beachieved in the field using a splice kit, such as the Lumenyte SpliceKit, and carefully following the instructions. Factory splicing may bean option. An optic cutter, such as Lumenyte's Optic Cutter, may beadvised for straight, clean, 90° fiber cuts. These fibers may beinstalled by removing approximately 4 inches (10 cm) of the outer jacket(not the fluoropolymer cladding) before inserting fiber into the lightsource. An end of the fiber may be near, but not touching theilluminator (light source) glass to assist in achieving maximumbrightness.

In some embodiments, an optical fiber of the present disclosure ismanufactured from a ESKA™ High-performance Plastic Optical Fiber: SK-10and SK-60 and/or ESKA™ Plastic Fiber Optic & Cable Wiring, manufacturedby Mitsubishi Rayon Co., Ltd., which are all available from MitsubishiInternational Corporation of New York, NY These optical fibers may eachconsist of a light transmitting PMMA (polymethylmethacrylate) core and afluorinated polymer as the cladding. It should be appreciated that theabove-described characteristics and properties of the optical fibers areexemplary and not all embodiments of the present disclosure are intendedto be limited in these respects.

In some embodiments, optical elements may be oriented in alignment withthe notches, cuts or openings in the nonlinear light-emitting portion ofan optical fiber of the present disclosure to adjust the light output.Such optical elements may include lenses, prisms, filters, splitters,diffusers and/or holographic films. The light source, and morespecifically, the optical fibers may have some or all of the propertiesand features listed in U.S. Pat. No. 6,289,150, which is herebyincorporated by reference in its entirety, as not all embodiments of thepresent disclosure are intended to be limited in these respects.

One or more optical elements, such as diffusers, polarizers, magnifyinglenses, prisms, holograms or any other element capable of modifying thedirection, quantity or quality of the illumination, individually or incombination can also be added and aligned with the core-clad, notchesand channel, track or holder and/or reflector.

Further, the implant may be designed to amplify light to the surroundingareas using one of reflective prisms within, Fresnel lens, Magnificationlens on the surface, shapes to the external form of the implant that aredesigned to magnify/amplify the light transmission.

The efficiency of plastic optical fiber is well known, with the lossesof light transmitted down the fiber almost nil. However, in the exampleof the fiber with the circumferential radial cuts on the fiber, there isstill a significant amount of light that is transmitted down the fiberand exits out the distal tip. This light is lost to the system, as it isend fire (a flashlight) versus the side fire (radial system describedherein). To maximize the efficiency of the system, a reflectivefitting/surface can be placed on the distal end of the fiber to reflectthe “end fire” energy back up and out of the side cuts of the fiber. Theuse of the reflective end cap results in approximately 7% increasedpower/efficiency of the system. The reflective material on the distalend of the fiber can vary, and can be in the form of a mirror, white orlight colored pigment, or other reflective surfaces. The loss in thesystem is decrease as the light emitted from the distal end of the fiberis reflected back into the fiber.

The surface of the reflector can be mirrored, or it can be an opticalwhite reflective surface. For example, labsphere's 6080 WhiteReflectance Coating is a diffuse white coating “paint” for reflectanceapplications covering the UV-VIS-NIR wavelength region. This coating isintended for customers with small-scale applications, those that requirea touchup to their original application, or those who wish to prototypecomponents using a high-reflectance white coating. This non-luminescentcoating yields reflectance values of 95 to 98% over the wavelengthregion from 300 to 1200 nm.

The 6080 is ideal for use in integrating spheres, reflectancespectrophotometers, sphere photometers, lamp housings, display backlightreflectors, optical components and other applications that call fordiffuse illumination or reflectance. This coating also allows LabsphereSpectraflect® and Duraflect® coated integrating sphere systems to betouched up in-between system recalibrations and re-coatings.

The 6080 coating is created in Labsphere's dedicated coating laboratoryusing the highest ISO-9001: 2000 procedures and requires no additionaldilution or mixing. The coating is packaged in airtight, containers andis shipped with surface preparation and application instructions.

Exemplary properties and performance of the system is reflected in thetables below. Reflectance is the percentage of light that is bouncedback from the mirror. Spectral range relates to the ability to handlewavelengths/ranges of NM frequencies. Thermal stability relates tomaximum temperature the system can handle. Laser damage relates to theamount of power the system can handle.

Reflectance: 95-98% (see chart below) Effective Spectral Range: 300 to1200 nm Thermal Stability: to 80° C. Laser Damage Threshold: 0.9 J cm⁻²

Wavelength Reflectance

(nm) % 400 0.970 500 0.975

Customized Cuts Along Optical Fiber to Align with Channel Configurationsto Maximize Light Amplification

FIG. 32 shows an embodiment of an optical fiber 306 of the presentdisclosure fabricated from a flexible light transmitting material thatcan be inserted into at least one channel. The optical fiber 306includes a hub 250 at a proximal end for attaching to a light source(either directly or indirectly, for example, through the use of anattachment system, see FIG. 1 ). The optical fiber 306 includes a linearelongated portion 248 for guiding light towards a nonlinearlight-emitting portion, generally referred to as 258, which emits lightfrom the outside of the fiber along its length. The nonlinearlight-emitting portion 258 can be any length suitable for a givenapplication. The distal tip of the optical fiber 306 may also emit lightcreating a small spotlight effect. In some embodiments, the opticalfiber 306 also includes a flexible strain relief 252 just to the rightof the hub 250 and a depth stop 254. In some embodiments, the strainrelief 252 prevents snapping of the optical fiber 306 at the hub 250junction. In some embodiments, the strain relief 252 and the depth stop254 are made from a flexible material. In some embodiments, the strainrelief 252 and the depth stop 254 are made from Santoprene™, athermoplastic rubber. FIG. 32 shows the optical fiber 306 in anelongated stretched condition and being in a “temporary” shape. In thetemporary shape, the nonlinear light-emitting portion 258 is stretchedand assumes a linear conformation in which the nonlinear light-emittingportion 258 of the optical fiber 306 can be advanced through the innerlumen of the elongated shaft of the balloon catheter 110.

Measurement has shown that a portion of light still emits from thedistal tip irrespective of the effect of the cladding being removed overa length of the fiber. The shorter the active length (i.e., the morepercentage of light is tip emitted), and the longer the active lengthless light is emitted. The ratios are approximately in the range of 5%to 20% of light delivered in a non-productive direction. In someembodiments, a plane or reflective tip on the end of the fiber can beused to resolve the loss and improve the efficiency. These mirrors canbe either front face or rear faced mirrors and can be a concave mirror.The result is that the light that is emanating out of the tip isreflected back into the fiber and increasing the efficiency of thesystem.

As illustrated in FIG. 32 , for example, according to some embodiments,a helical design may be provided that includes cuts at a most proximalportion of the light-emitting portion that are spread farther apart thancuts at a most distal portion of the light-emitting portion. Typically,when an optical fiber is attached to a light source that is “on”, thecuts at the proximal portion of the light-emitting portion will emitlight that looks brighter than the cuts at the distal portion of thelight-emitting portion when in at least one channel.

The optical fiber may include a non-shape memory optical fiber or ashape memory optical fiber depending on the application relating to oneor more channels or not relating to one or more channels located withinor on the outer surface (i.e. within ridges) of the expandable member.For example, it may be desirable to provide shape memory to thelight-emitting portion of an optical fiber of the present disclosure soas to conform to a shape of at least one channel. In some embodiments,the shape memory can be imparted to the light-emitting portion usingconventional techniques known in the art. By way of a non-limitingexample, a distal length of an optical fiber of the present disclosuremay first be heat treated to provide stress relief, that is, to removeany shape memory from the optical fiber induced into the optical fiberduring the manufacturing process. Heat treatment can also be used toinduce a pre-set into the optical fiber. The distal length of thestress-relieved optical fiber may then be wound around a circularmandrel to provide the distal length with a desired shape. Next, themandrel with the coiled optical fiber can be subjected to heat treatmentto induce the desired shape and then quenched to set the desired shapeinto the optical fiber. In an embodiment, the optical fiber may be heattreated using a water bath.

FIG. 33 shows a view of another embodiment of a distal end of a ballooncatheter of the present disclosure, which is similar to FIG. 26 ,wherein the optical fiber 306 has a pre-defined shape specific to theshape of the channel 303A. Wherein the optical fiber 306 can beincorporated within the elongated shaft of the balloon catheter andencircle the inner surface 330 of the expandable balloon 303A within thechannel 303A.

The nonlinear light-emitting portion can be any given length suitablefor a given application. For example, a nonlinear light-emitting portionof an optical fiber of the present disclosure can have a length rangingfrom about 60 mm to about 300 mm, 60 mm to about 400 mm, 60 mm to about500 mm or 60 mm to about 600 mm. It is contemplated the optical fibermay be shaped to incorporate a single loop to extend an entire length ofthe channel 303A or only partially extend the entire length of thechannel 303A.

It is possible illuminators may be made in the optical fiber core alonebefore the cladding is added and/or the illuminators may be made in thecladding and the core after it has been surrounded by the cladding. Insome embodiments, when the cladding is heated to tightly shrink aroundthe core, the cladding may affect the uniformity of the illuminators inthe core by either entering the notch or closing the cut therebyreducing the potential light deflecting properties of the illuminator.

The illuminators may be positioned to direct light across the greaterdiameter of an elliptical optical fiber core out and out through aregion opposite from each of the respective illuminators. This may beaccomplished by angling the notches and/or cuts to direct light from thelight source through the optic core. The illuminators allow bettercontrol of escaping light by making the notches, which are positioned onone side of the optic to direct the light rather than allowing the cutsto reflect/refract light in various directions which reduces thecontribution of light to a desired focusing effect.

In an embodiment, the total light output from a nonlinear light-emittingportion of the present disclosure having a length of about 100 mm is thesame as a nonlinear light-emitting portion of the present disclosurehaving a length of about 300 mm. In an embodiment, the total lightoutput required for the nonlinear light-emitting portion of an opticalfiber of the present disclosure is about 10 μW/cm², 20 μW/cm², 30μW/cm², 40 μW/cm², 50 μW/cm² or 60 μW/cm².

In some embodiments, the optical fiber may include an optical fiber coresurrounded by cladding material and one or more illuminators. Theilluminators may be of uniform size and shape positioned in apredetermined, spaced-apart relation, linearly, along a side of theoptical fiber core. The optical fiber core may be received in a trackand/or holder and/or reflector comprising a channel constructed with areflective interior surface centered about the illuminators. The holderand/or reflector may be positioned adjacent to or in contact with theplurality of illuminators.

Irrigation

In some embodiments, the system can include mechanism for providingirrigation to the treatment site. In some embodiments, hydrogen peroxidecan be used in conjunction with the light so that enhanced kill isperformed. The concentration of the H2O2 may vary, and in someembodiments can be of a 3-9% concentration. The system can include theability to provide irrigation to the canal of H2O2 during theillumination of light. The system can also include the ability toprovide irrigation to the canal after the illumination of light to thecells so that the H2O2 is able to permeate the cell in their weakenedstate. In some embodiments, the balloon has a ridge on it at the lowerpoint so that the H2O2 that is infused is held in a surrounding columnof fluid around the balloon and that the fluid doesn't fall below theillumination point. The lower aspect of the balloon can include anaspiration port where the top if the balloon has an irrigation/infusionport. The combination of the two allows for the continual drip of fluidsduring the illumination procedure to ensure that the fibers and thelight emitted do not become occluded by blood or other intramedullarymaterials. The fluid, such as H2O2, can be delivered near or adjacent tothe blue light so that the two functions are combined and enhanced.

Methods of Delivering Light to Cavities of the Bone to Provide anAnti-Microbial Effect

FIG. 34A, FIG. 34B, FIG. 34C, FIG. 34D and FIG. 34E provide embodimentmethods for delivering light and/or implanting an intramedullary implantof the present disclosure within the intramedullary space of a weakenedor fractured bone. A minimally invasive incision (not shown) may be madethrough the skin of the patient's body to expose a fractured bone 1102.The incision may be made at the proximal end or the distal end of thefractured bone 1102 to expose the bone surface. Once the bone 1102 isexposed, it may be necessary to retract some muscles and tissues thatmay be in view of the bone 1102. As shown in FIG. 34A, an access hole1110 may be formed in the bone by drilling or other methods known in theart. In some embodiments, the access hole 1110 has a diameter of about 4mm to about 7 mm. In some embodiments, the access hole 1110 has adiameter of about 9 mm.

The access hole 1110 extends through a hard compact (cortical) outerlayer 1120 of the bone into the relatively porous inner or cancelloustissue 1125. For bones with marrow, the medullary material should becleared from the medullary cavity prior to insertion of the presentlydisclosed device. Marrow is found mainly in the flat bones such as hipbone, breastbone, skull, ribs, vertebrae and shoulder blades, and in thecancellous material at the proximal ends of the long bones like thefemur and humerus. Once the medullary cavity is reached, the medullarymaterial including air, blood, fluids, fat, marrow, tissue and bonedebris should be cleared or loosened to form a void. The void is definedas a hollowed out space, wherein a first position defines the mostdistal edge of the void with relation to the penetration point on thebone, and a second position defines the most proximal edge of the voidwith relation to the penetration site on the bone. The bone may behollowed out sufficiently to have the medullary material of themedullary cavity up to the cortical bone removed. There are many methodsfor removing the medullary material that are known in the art and withinthe spirit and scope on the presently disclosed embodiments. Methodsinclude those described in U.S. Pat. No. 4,294,251 entitled “Method ofSuction Lavage,” U.S. Pat. No. 5,554,111 entitled “Bone Cleaning andDrying system,” U.S. Pat. No. 5,707,974 entitled “Apparatus forPreparing the Medullary Cavity,” U.S. Pat. No. 6,478,751 entitled “BoneMarrow Aspiration Needle,” and U.S. Pat. No. 6,958,252 entitled“Apparatus for Extracting Bone Marrow.”

A guidewire (not shown) may be introduced into the bone 1102 via theaccess hole 1110 and placed between bone fragments 1104 and 1106 of thebone 1102 to cross the location of a fracture 1105. The guidewire may bedelivered into the lumen of the bone 1102 and may cross the location ofthe break 905 so that the guidewire spans multiple sections of bonefragments. As shown in FIG. 34B, the expandable member 170 of thedelivery catheter 101 for repairing a fractured bone, which isconstructed and arranged to accommodate the guidewire, is delivered overthe guidewire to the site of the fracture 1105 and spans the bonefragments 1104 and 1106 of the bone 1102. In some embodiments, theguidewire can be used to delivery additional instruments down the canal.

In some embodiments, it is contemplated that at least one optical fiberor other light source may be introduced into the bone for a period oftime prior to placing the expandable member 170 within the cavity of thebone to provide for an anti-microbial effect. That is, in someembodiments, the bone 1102, the cavity 1110, and/or the surroundingtissue can be pre-illuminated to substantially sterilize the repair siteprior to introduction of the expandable member. In some embodiments,because the pre-illumination light source does not need to pass throughthe balloon catheter 110, the pre-illumination light source can be alarger, higher-powered light source than the in-process light source forgreater initial anti-microbial effect.

In some embodiments, the guidewire can be placed by use of a splitsheath and dilator (not shown). In some embodiments, the split sheathand dilator can include an outer tube-shaped sheath and an inner dilatorextending coaxially through the sheath. In some embodiments, the innerdilator can include a passageway sized and shaped for passing theguidewire therethrough. In some embodiments, the guidewire, the sheath,and/or the dilator can include at least one optical fiber or other lightsource for illuminating the repair site. In some embodiments, thesheath, the dilator, and/or the guidewire can thereby be used topre-illuminate the repair site, illuminate the repair site duringinstallation of the expandable member 170, and/or to illuminate therepair site during curing and hardening of the expandable member 170.Thus, by providing light source integrated within the sheath, dilator,and/or guidewire, a duration of the illumination of the repair site canbe increased, thereby improving the anti-microbial effect.

Once the expandable member 170 is in place, the guidewire may beremoved. The location of the expandable member 170 may be determinedusing at least one radiopaque marker 1190 which is detectable from theoutside or the inside of the bone 1102. Once the expandable member 170is in the correct position within the fractured bone 1102, a deliverysystem which contains optical fiber(s) passes light from a light sourcethrough the first port 162, through the inner lumen of the elongatedshaft of the balloon catheter 110, through the distal end 104 of theballoon catheter 110, through the inner lumen of the expandable memberand into the cavity of the bone. It is contemplated the optical fiber(s)may pass through a channel located within the expandable member. It isalso possible the optical fiber(s) may pass through a manifold locatedin the inner lumen of the expandable member and then into a channellocated within the expandable member. It is possible for the opticalfiber(s) to enter a channel located within a ridge positioned on anouter surface of the expandable member.

It is possible for radiopaque markers and guides to provide alignmenttowards steering the user towards a correct position. Further, the endof the implant may have a longer inner tube and light guide receptaclethat is longer than the implant and extends several inches beyond.Further still, this end could be left attached to the implant and buriedsubcutaneously and sealed, so that when and, if needed, the end wasexposed via a small incision, the rolled tube exposed and the lightfiber introduced would all make for the delivery to be easier.

As the fibers are radiolucent, it would be difficult to know theplacement of the fibers or to visualize the fibers, so the radiopaquemarkers on the distal tip of the fiber and/or the proximal end of thefiber, can be used to ensure that the fibers are placed appropriatelywithin the canal.

Once the optical fiber(s) is positioned within the cavity of the bone,the optical fiber(s) is capable of providing for an anti-microbialeffect, either prior to, during the delivery of the light-sensitiveliquid, or after the light-sensitive liquid has been cured and hardened.It is contemplated the optical fiber(s) may provide for an antimicrobialeffect while a fluid, such as water, air, or a light-sensitive liquid isinfused through the inner void 210 in the delivery catheter 101 andenters the inner cavity 295 of the expandable member 170.

In some embodiments, after the expandable member 170 is in the correctposition within the fractured bone 1102, a delivery system whichcontains a light-sensitive liquid is attached to the port 195. Thelight-sensitive liquid is then infused through the inner void 210 in thedelivery catheter 101 and enters the inner cavity 295 of the expandablemember 170. This addition of the light-sensitive liquid within theexpandable member 170 causes the expandable member 170 to expand, asshown in FIG. 34C. As the expandable member 170 is expanded, thefracture 1105 is reduced. Unlike traditional implants, such as rods,that span the fracture site, the expandable member 170 of the presentdisclosure does more than provide longitudinal strength to both sides ofthe fractured bone. In some embodiments, the expandable member 170having the design can be a spacer for reducing the fracture and forholding the fractured and compressed bones apart at the point of thecollapsed fracture.

Once orientation of the bone fragments 1104 and 1106 are confirmed to bein a desired position, the light-sensitive liquid may be hardened withinthe expandable member 170, as shown in FIG. 34D, such as by illuminationwith a visible emitting light source. In some embodiments, during thecuring step, a syringe housing a cooling media may be attached to theproximal end of the delivery catheter and continuously delivered to theexpandable member 170. The cooling media can be collected by connectingtubing to the distal end of the inner lumen and collecting the coolingmedia via the second distal access hole. After the light-sensitiveliquid has been hardened, the light source may be removed from thedevice. Alternatively, the light source may remain in the expandablemember 170 to provide increased rigidity.

In some embodiments, subsequent illumination of the bone 1102 andsurrounding tissue of the repair site can be performed after theexpandable member 170 has been hardened. In some embodiments, where thelight source has been removed from the expandable member 170, suchsubsequent illumination can be performed by reintroducing the lightsource into the hardened expandable member 170 and activating the lightsource. In some embodiments, where the light source has been removedfrom the expandable member 170, such subsequent illumination can beperformed by positioning a light source adjacent to the hardenedexpandable member 170 and directing illumination into the expandablemember 170 for distribution throughout the repair site. In someembodiments, where the light source remains in the expandable member 170(e.g., to provide rigidity as discussed above), the light source can bereactivated to illuminate the repair site. In some embodiments,reactivation of the remaining light source can include reconnecting thelight source to an external power or light generating device. In someembodiments, the remaining light source can include a power source(e.g., batteries) for remote activation as needed. In some embodiments,the remaining light source can include inductive circuitry for example,for inductively activating the light source and/or for inductivelycharging batteries of the light source.

FIG. 34E shows at least one embodiment of a bone fixation device in acavity of a bone after being separated from an introducer. For example,the expandable member 170 once hardened, may be released from thedelivery catheter 101 to form a photodynamic bone fixation device insidethe intramedullary cavity of the bone 1102. It is contemplated thatoptical fiber(s) may be passed in an inner lumen of the photodynamicbone fixation device, and optionally pass through a manifold locatedwithin the inner lumen and into a channel located in the photodynamicbone fixation device. Further, it is possible optical fiber(s) may bepassed in a channel located within a ridge positioned on an outersurface of the photodynamic bone fixation device. Once the opticalfiber(s) are positioned with the cavity of the bone, the opticalfiber(s) may provide for an anti-microbial effect.

Applications/Uses for ABLP

While the use of ABLP can be used to address the use of the technologyin medical indications, the efficiency of the system allows use innon-traditional applications.

In some embodiments, the system can be used to resolve antimicrobialload in high contact areas (e.g., escalator hand holds, elevators, otherhigh touch contact areas) through the illumination of the blue light tothe surface area.

In some embodiments, light sources can be used with personal waterbottles where potable water may not be available. For example, fibersand light sources can be embedded in water bottles to kill bacteria.

In some embodiments, light sources can be embedded in cookingpreparation tables to ensure that bacterial isn't capable of growth.

In some embodiments, light sources can be used to cover harvested foodcrops that may be susceptible to bacteria, such as E coli breakouts(e.g., lettuce).

While orthopedics is described in detail above, the use of the lightsource can be applicable to other surgical and medical proceduresincluding but not limited to those medical uses described below.

Dermatology—Blue light has been shown to be effective in the treatmentof acne. Acne vulgaris is a chronic inflammatory disorder of thepilosebaceous unit affecting more than 85% of adolescents and oftenpersisting into later adulthood. Conventional therapy with antibioticsand retinoids yields mixed results and can be complicated by antibioticresistance and adverse treatment profiles. Therefore, newer therapeuticmodalities such as light-based therapy have been developed to addressthe need for acne treatment. A variety of narrowband light sources,intense pulsed light (IPL), lasers, and photodynamic therapy (PDT) havebeen studied. Treatment with these light sources may offer improvementsin inflammatory acne and acne scarring, with more limited benefit fornoninflammatory (comedonal) acne.

Mechanism of action of light-based therapies—Previous clinicalobservations and studies have shown that patients experience acneimprovement after exposure to natural sunlight but the specificmechanism had not been elucidated. More recently, it has been postulatedthat light-based therapies work to decrease Propionibacterium acneslevel and reduce pilosebaceous unit size and function. Specifically,light is absorbed by porphyrins produced naturally within sebaceousfollicles by P. acnes. Porphyrins (coproporphyrin III and protoporphyrinIX) absorb light wavelengths between 400 and 700 nm with 415 nmwavelength within the blue light spectrum being most effectivelyabsorbed. Light absorption leads to photo-excitation of porphyrins andsubsequent release of singlet oxygen and reactive free radicals thatexert bactericidal effects on P. acnes. Longer wavelengths, such as redlight, activate porphyrins less effectively but penetrate deeper intothe skin where it may directly target sebaceous glands and exertanti-inflammatory properties by influencing cytokine release frommacrophages. Blue light has also been shown to exert anti-inflammatoryeffects in keratinocytes.

The use of light and laser in the treatment of acne is increasing asthese modalities are safe, effective, and associated with no or minimalcomplications when used appropriately. These light and laser sources arealso being used in combination with pharmacological and/or physicalmeasures to synergize their effects and optimize the therapeuticoutcome.

Blue light acne treatment is administered via a blue light deliverysystem, such as in a mask to reduce distance between the treatment siteand the light. The procedure simply involves a patient sitting in frontof a blue light lamp for about 15 minutes.

In some embodiments, light fibers are woven into a fiber/mask or othercontact form such that the patient applies the shape to the affectedarea, as shown in FIG. 35 and FIG. 36A and FIG. 36B. The intimatecontact can ensure even power distribution. In some embodiments, thelight fibers can be applied to a clear fluid mask where the light fibersare encased in a form fitting mask. The light can be transmitted throughthe mask material to the affected skin.

ENT Applications—Blue light can also be applied in the ear, nose andthroat (ENT). For example, chronic rhinosinusitis (CRS) is a commonchronic condition that can benefit from antimicrobial photodynamictherapy (aPDT), a noninvasive nonantibiotic broad spectrum antimicrobialtreatment. aPDT can be used to treat CRS polymicrobial antibioticresistant Pseudomonas aeruginosa and MRSA biofilms in a maxillary sinuscavity model.

Bandages—Light fibers can be woven into a material that is used for awound bandage. For example, the bandage can be a matrix of fibers withlinear fibers in a single direction, a cross hatch “checkerboard” offibers, or a spongy mass of fiber where the light source is attached toa coiled/ball/mass of light fibers. The bandage can include one or moreports to energize the fibers in the bandage, or can include a battery.

Direct effects of light on pain and inflammatory mediators such ashistamine, serotonin, bradykinin, and prostaglandins have beendocumented. Further, light treatments can promote epithelial migrationand proliferation, endothelial migration and organization forangiogenesis, inflammatory infiltration, macrophage phagocytoses, immunesurveillance, fibroblast matrix synthesis, and wound contraction, amongother things. For example, light treatments can be used to promoteepithelial cell functions, especially their basal colony-forming units(stem/progenitor cells) that not only can aid re-epithelialization butalso promote regeneration of skin appendages such as glands and hairfollicles.

Chronic wounds—Chronic wounds are defined as wounds that do not heal forat least 180 days (3 months) and do not proceed through the normalreparative process. These wounds usually present with lack of tissueintegrity and volume, pain, and persistent inflammation and are ofteninfected. The initiating injury in these wounds can vary from physical(pressure, burns, or radiation), chemical, electrical, or immunologicinjuries that all result in persistent tissue damage). These wounds canbe illuminated either via a traditional bandage with light fibersembedded. For example, the light fiber illumination system is batteryoperated system, allowing for patient mobility and the ability for thepatient to maintain their activities of daily living without encumberageto plug in power units.

The fibers can also have a physical benefit to the bandage as theabsorbent materials of a bandage can be mounted above the fibers. Thefiber diameter can act as a spacer with the wet fluids of the woundbeing drawn up and away from the wound site while the surfaceillumination provides a treatment modality for these issues. The smoothsurface of the fiber can also preclude ingrowth and incorporation intothe tissue healing matrix.

Many chronic wounds are “wet” which has been shown to assist in healing,prevent skin breakdown. However the “wet” nature off the wound alsoallows for a rich environment for infection. The application of the bluelight can assist in the healing while preventing the potential forinfection/bacterial growth. The blue light applied to the wet wound areacan help to reduce the potential for a pooled area of bacteria.

Venous Ulcers, Pressure Ulcers, and Diabetic Foot Ulcers—Diabetic footulcers, being notoriously difficult to cure, are one of the most commonhealth problems in diabetic patients. There are several surgical andmedical options already introduced for treatment of diabetic footulcers. Blue light can be used as a treatment option for open wounds.

Bone—As mentioned above, ABLP can be used in a variety of procedures. Insome embodiments, ABLP can be used in treatment of bone, either insideor outside the bone. The treatment of infections may not be limited tothe interior of the bone, and there may be cases where the externalportion of the bone is infected. The application of the light to treatthe infections needs to be in close proximity to the afflicted area,hence methods and means to deliver light must be adjusted to thespecific indications.

Osteomyelitis is inflammation of the bone caused by an infectingorganism. Although bone is normally resistant to bacterial colonization,it can get infected in multiple ways. The infecting organism may reachbone through blood or events such as trauma, surgery, the presence offoreign bodies, or the placement of prostheses that disrupt bonyintegrity and predispose to the onset of bone infection. When prostheticjoints are associated with infection, microorganisms typically grow inbiofilm, which protects bacteria from antimicrobial treatment and thehost immune response.

Infectious periostitis is the term used for infection that invades theperiosteum only and does not involve the cortex and bone marrow. Withinfectious (or suppurative) periostitis the changes are subtle and maybe identified by a periosteal reaction. As the infection penetrates intothe cortex but does not invade medullary bone, the term infectiousosteitis is used. Once the infection involves both cortex and bonemarrow, the more accurate term is osteomyelitis.

The term septic arthritis is used to describe infection of a joint.Joint infection, such as Staphylococcus aureus, erodes cartilage anddecreases joint mobility.

Osteomyelitis secondary to contiguous soft tissue or by direct extensiondepends on the mechanism of transmission. For example, a puncture woundis most commonly affected by Staphylococcus or Pseudomonas, whereas ananimal bite from a dog or a cat can cause an infection from Pasteurellamultocida. Pseudomonas is also seen in nosocomial infections.

Fungal osteomyelitis may mimic bacterial or tuberculosis infection ofbone both clinically and radiographically.

As the bone is encased and surrounded in tissue, muscle, etc., a meansof delivery of the light fiber to these areas may include the use of along thin hollow cannula with a sharpened tip, that allows the lightfiber to be inserted. The cannula is delivered within the specificlocation of the infection, and the cannula withdrawn, leaving the fiberin place.

In some embodiments, the system can be used with minimally invasive softtissue delivery. Within the capsule of the bone (e.g., joint), the fibercan be delivered into tissues surrounding/adjacent/into joints. Thefiber can be loaded into a large bore hollow needle (such as biopsyneedle diameter, or other thin walled metal/plastic cannula that can beused to deliver the fiber). The cannula can be positioned in the tissueand then withdrawn while the fiber is held in position (the cannablepulled back over the fiber), The fiber can be illuminated in placeswhere it could not be typically delivered without largeinvasive/exposing surgery.

In some embodiments, ABLP can be used prior to the application of a boneplate, or after the application of a bone plate to treat an infectedbone plate. The fiber may similarly require placement in contact with,in proximity to external fracture stabilization plates, e.g., femur,tibia, fibula, ulna, radius, and distal radius plates.

The light fiber can be placed in close proximity to these externalplates, held in position by suture that is affixed to the plate andsurrounding the fiber and ensuring a position close to the plate andclose to the infection. In some cases, where the plate is not held intight apposition to the bone (e.g., a locking plate vs a compressionplate), the light fiber may be able to be positioned under the plate toilluminate the space between the plate and the periosteal surface.

In some embodiments, ABLP can be used in a trauma situation, forexample, in the treatment of an open wound or a broken bone. Forexample, in trauma indications, the patient/afflicted area/openwound/compound breaks where the bone is exposed to external pathogenscan be wrapped/encased in a wrap/bandage/protective dressing on top ofthe wound to prevent the growth/transmission of bacteria.

External fixtures, such as ones made of metal or polymer frames, can beattached to the bone or can be percutaneously penetrating the skin anddriven into the bone as a means to provide stability to the bone whilehealing. For example, a “shanz screw” can be used and is driven into thebone and resides/exits the skin to provide attachment to one or morecross fixation bars This screw that exits the skin can be a locationpoint for infection to migrate from skin to bone. A light and/or lightfiber can be attached to the external part of the screw to illuminatethe screw and/or tissue interface to prevent bacterial growth.

In some embodiments, the light source can be mounted at both ends of thefiber, for example in those indications where long lengths of fiber maybe needed or the fiber is very thin (e.g., the bandage concept—the steelwool/fluffy mass of fibers) multiple light sources can be added to thefiber. This confirmation of light sources can be used with any of theembodiments disclosed herein.

In some embodiments, ABLP can be used in orthopedic applications,including but not limited to the knee, ankle, shoulder, elbow, wrist andfoot.—joints (infections in synovial fluid of a joint)

Ear Infections—In some embodiments, a probe can be attached to a lightsource, and the probe with one or more optical fibers can be deliveredto the ear canal. For example, the probe can be delivered to the middleear, just behind the eardrum. The light can be directed to the infectedear, emitting light from the device into the ear canal, exposing thecanal to sufficient light to reduce or eliminate the infection.

Gynecology/Urology—In some embodiments, ABLP can be used ingynecological applications. For example, a vaginal speculum or othervaginal dilator of clear, translucent materials can have one or morelight fibers/light delivery embedded therein and can be used towards thetreatment of gonorrhoeae or other gynecological issues.

The system can also be used in urology applications, such as in theurinary track or inside a catheter. For example, catheter-associatedurinary tract infections are the most common hospital-acquiredinfection, for which Escherichia coli is the leading cause. The use ofblue light from 405 to 470 for inactivation of E. coli attached to thesilicone matrix of a urinary catheter. The use of a dual lumencatheter—where the light fiber is placed within a small 1.7 mm lumenthat has a clear pathway to allow light to be delivered within the mainlumen of the catheter (for urinary fluids). The use of a multi lumencatheter, where the light fibers are placed within small 1.7 mm lumenthat has a clear pathway, allows light to be delivered within the mainlumen of the catheter (i.e., for urinary fluids). Note that the two ormore fibers may be more effective as only the interior portion of thelight fiber is delivering light to the internal lumen of the catheter.

In some embodiments, a catheter based delivery system can be placed andleft in position while a urinary catheter is in place and then removed.When the urinary catheter needs to be removed/replaced with a new one,the component for light delivery can be left in place. In someembodiment, urinary catheters for men may have one fiber placed withinthe catheter and one fiber that is placed around the catheter at thepoint of entry to the urethra to preclude bacteria transmission on thesurface of the catheter from entering the body. This can form a layeredstacked system having a fiber within the lumen of the catheter. When thecatheter is placed within the urethra, there is a secondary lightsource/fiber to kill the potential bugs that would be entering the spaceurethra—catheter junction. This allows for light coming from within andlight emitting at the junction point.

Respiratory Applications—In some embodiments, ABLP can be used inrespiratory applications, for example, relating to the trachea or aventilator. For example, critically ill patients can contractventilator-associated pneumonia. This nosocomial infection increasesmorbidity and likely mortality as well as the cost of health care. Xrayor MM can be taken to discern the location of a pneumonia, and the lightfiber can be delivered via a bronchoscope or other device to theaffected area, where the diseased tissue illuminated. Similarly a fiberresiding in an endotracheal tube or other ventilator tubing can be usedto mitigate any buildup of bacteria.

It should be noted that light can be delivered to any to internal tissueor orifice (i.e., percutaneous delivery). In some embodiments, a usercan take an image, including Xray and MRI, to discern the location ofthe light delivery mechanism and the tissue and/or bone to be treated.the fiber shall have a radiopaque marker/markers on it so as to providevisualization to the user in defining the position/location of thefiber. The use of ancillary instrumentation towards delivery andguidance may be used, both for placement and for subsequent directionand/or adjustment of the fiber, such as components that allow for asteerable distal end.

Examples

The following paragraphs provide experiments regarding the presentdisclosure relating to killing of orthopedic relevant pathogens usingblue light.

Overview

It is believed that blue light with wavelengths outside of the UVspectrum can have antimicrobial properties for both Gram-negative andGram-positive bacteria. Currently, a clinical trial using blue light forphotodynamic bone stabilization has begun, in accordance with aspects ofthe present disclosure. The question of whether the blue light used forphotodynamic bone stabilization could kill orthopaedic relevant bacteriawas asked because one of the major outputs from the optical fiber atspectrum of visible blue or violet light wavelengths (see FIG. 37 ) hasbeen shown to eradicate methicillin-resistant. FIG. 37 illustrates anexemplary graph showing the output (line 520), positive control (405nm—line 522), positive control (470 nm—line 524). The box areahighlights the wavelengths of light (405 nm to 470 nm) that has shown tobe antimicrobial against orthopaedic relevant bacteria. The blue lighthas a major peak in the region of 405 nm. While experimental resultsfocused on wavelength of 405 nm, even better results are obtained byusing multiple frequencies of blue light or a spectrum of visible blueor violet light wavelengths. For example, 4 of 5 frequencies can bepushed down the same fiber by individual LEDs (each individuallycontrolled). It will be understood that any number of light frequenciescan be used, including 10, 20, 100 or more. These various frequenciescan be used associated with different bacteria, including but notlimited to MRSA, Staphylococcus, Streptococcus, Enteroccocous,Psuedomonas, and Candida.

TABLE 1 Microbe of Interest Wavelength Radiant exposure Inactivationefficacy MRSA 415 168 4.82-log10 CFU MRSA 412   28.5 72% MRSA 450   28.581% MRSA 405 121 91.20%   MRSA 465   112.5 >2-log10 CFU MSSAStaphylococcus 400  50-108 >5-Log10 CFU Staphylococcus 405 133 5.20-6.27log10 CFU Staphylococcus 405 118-214 >4-log10 CFU Streptococcus 405 1335.20-6.27 log10 CFU Streptococcus 405 137-260 3.2-4.3log10 CFUEnteroccocous (including VRE) 405  118-2214 >4-log10 CFU Enteroccocous(including VRE) 400  50-108 >5-log10 CFU Pseudomonas 400 50-180 >5-Log10 CFU Pseudomonas 415 110 7.64-log10 CFU Pseudomonas 470480 92.40%   Pseudomonas 405 133 5.20-6.27 log10 CFU Pseudomonas 405 118-2214 >4-log10 CFU Pseudomonas 470  80-180 47% to 2.87-log10 CFUCandida 405 288-576 5-log10 CFU Candida 415  70 5.42-log10 CFU Candida405 332 4.52-log10 CFU

TABLE 2 Summary of blue light inactivation of bacteria in vitro Lightsource Radiant exposure Bacterial species/strains Inactivation efficacy407-420 nm metal 374 J/cm² at lamp P. acnes 15.7% reduction in CFUimmediately halide lamp aperture; lamp-target after irradation; 24.4%reduction 60 distance: 25 cm. min after irradiation 407-420 nm intense75-225 J/cm² P. acnes 2 log₁₀ at 75 J/cm², 4 log₁₀ at 150 J/cm², lightlamp and 5 log₁₀ at 225 J/cm². 405-nm diode laser 20 J/cm² H.pylori >99.9% 405 nm light- 15 J/cm² at lamp P. gingivalis   >75%emitting device aperture 380-520 nm 4.2-42 J/cm² P. gingivalis, P. P.intermedia and P. nigrescens >5 log₁₀ broadband light intermedia, P.nigrescens, at 4.2 J/cm²; P. melaninogenica >5 P. melaninogenica, and S.log₁₀ at 21 J/cm²; P. gingivalis 1.83 Constellatus log₁₀ at 42 J/cm².400-500 nm light Irradiance between P. gingivalis, F. The minimalinhibitory dose for P. lamps used for 260 and 1300 mW/cm² nucleatum, S.mutans, gingivalis and F. nuncleatum was 16-62 dental restoration for upto 3 min and E. faecalis J/cm², for S. mutans and E. faecalis was159-212 J/cm². 405-nm 50.4-55.2 J/cm² at MRSA USA 300; MRSA 92.1% forUSA 300; 93.5 for IS-853 superluminous lamp aperture; lamp- IS-853 diodelight target distance: 1-2 min 470-nm 55 J/cm² at lamp MRSA USA 300;MRSA 90.4% for both strains superluminous aperture; lamptarget IS-853diode light distance: 1-2 min 405 and 470 nm 15 J/cm² S. aureus, P.aeruginosa S. aureus 90% at 405 nm, 62% at 470 light nm; P. aeruginosa95.1% at 405 nm, 96.5% at 470 nm.

Null Hypothesis

Blue light is not capable of bactericidal activity against orthopaedicrelevant bacteria because it does not have enough energy to bebacterial.

Objective

Using suspension cultures, we will test the following: (1) Does lightkill MSSA and MRSA in a time dependent manner? (2) Does light killpatient isolated bacterial from orthopaedic infections? and (3) Does theimplant have bactericidal activity during the time required forintra-operative polymerization (about 15 minutes)?

Significance

It is possible blue light may indicate that broad-spectrum antimicrobialeffects that can be generated for both Gram-negative and Gram-positivebacteria. The antimicrobial effect may be due to bacteria intracellularporphyrins and the production of cytotoxic reactive oxygen molecules.Light in the visible spectrum may have the most effective wavelength forantimicrobial effects with the region of about 402-420 nm, which appearto be most promising. It is encouraging that one of the major peaks foremission is in this blue light region (see FIG. 37 ). However, the bluelight inactivation of bacteria may be dependent on dose. The dose oflight needed to be bactericidal may be determined by an equation E=Pt,where E is in J/cm², P is in mW/cm² and t is time in seconds. It wasdetermined from previous studies that a dose of 36 J/cm2 is toxic tobacteria but not harmful to mammalian cells.

Initial suspension culture experiments were conducted demonstrating atime-dependent killing of MSSA with the light at energy levels that arenot toxic to mammalian cells (see FIG. 38A and FIG. 38B). Furthertesting will allow for further characterization of this effect onpatient isolated from orthopaedic infections and to test the potentialbactericidal effect during a 15 minute implant curing process.

Research Design and Method

Suspension cultures have been used to determine the effect of blue lighton bacterial inactivation. This method is used to study the effect ofblue light on MSSA ATCC 29213. The bacterial strain was diluted in 0.9%NSS until reaching an optical density of 0.5 McFarland units (1.5×10⁸CFU/ml). Initial experiments were completed to determine the correctserial dilution in NSS to obtain about 200 colonies per 100 ul inoculumonto 100 mm blood agar plates (see FIG. 38A and FIG. 38B for colonycounts). After final dilutions to a concentration that is relevant tocause orthopaedic related infections (around 10⁵), 3 ml of bacterialsuspension was used for the light dosing experiments. A “end fire” fiberoptic cable and R&D light box were included and then the intensity oflight emitted from the end of the fiber optic cable to be 17.4 mW/cm² inthe wavelengths from about 395-415 nm was calculated. This “end fire”cable was used for the dosing experiments.

From a distance of 2 cm above the suspension culture surface the “endfire” light was delivered to the culture. 100 ul samples were takenafter vortexing at 0, 5, 10, 15, 20, 25 and 30 minutes of continuouslight treatment with duplicate experiments performed. The 100 ulbacterial suspension samples were streaked onto 100 mm blood agar platesand immediately placed into an incubator for 24 hrs at 37° C. at 5.5%CO₂. After 24 hrs the plates had colonies counted and data presented as% kill over time. Several controls were used including a 30 minutecontrol of bacterial suspension in the 0.9% NSS with plating and colonycounts that were not different from the 0 minute control indicating noeffect of diluent over time. Additionally, since light generates heatthe bacterial suspension cultures had direct temperature measurements.This did show that the suspensions increased from room temperature to26.2° C. during the 30 minute treatment time indicating that thedecrease in colony counts were not due to temperature effects. Initialexperiments were done in a hospital microbiological laboratory.

It is noted the implant takes 15 minute for the polymerization step. Itis therefore encouraging that the data in FIG. 38A and FIG. 38B indicatea bactericidal effect within this timeframe. The experiment showed tokill orthopaedic relevant bacteria.

FIG. 39A, FIG. 39B, FIG. 39C, and FIG. 39D show the initial experimentalset up. FIG. 39E indicates heat generation issues with change to opticalfiber (POF). FIG. 39F indicates the identified wavelength viaexperimentation is about 405 nm. FIG. 39G indicates through results ofexperimentation that blue light works to have an anti-microbial effecton bones.

FIG. 40A, FIG. 40B, FIG. 40C, FIG. 40D, FIG. 40E, FIG. 40F, FIG. 40G,FIG. 40H, FIG. 40I, FIG. 40J, FIG. 40K, FIG. 40L, FIG. 40M, FIG. 40N,FIG. 40O, and FIG. 40P show the optical fiber (POF) experimental set up.FIG. 40A and FIG. 40B indicate MRSSA, ATCC29213, dilution in NSS, 3 cmdistance from optical fiber (POF), 5, 10, 15, 30, 45 and 60 minute time.Plating over time of 100 ul, blood agar. FIG. 40C shows patient isolatedcultures treated with blue light. FIG. 140D shows a graph resulting in a100 percent kill rate of MSSA with a device.

FIG. 40E and FIG. 40F indicate MRSSA, ATCC29213, dilution in NSS, 2 cmdistance from the optical fiber (POF), 5, 10, 15, 20, 25 and 30 minutetime. Plating over time of 100 ul, blood agar and additional control.FIG. 40G shows patient isolated cultures treated with blue light. FIG.40H shows a graph resulting in a staph aureus kill rate over time. FIG.40I and FIG. 40J show the percent decrease in colony counts versus time.

FIG. 40K and FIG. 40L indicate the Oct. 23, 2015 trial that included:Patient isolate MRSA, dilution in NSS, 2 cm distance from the opticalfiber (POF), 5, 10, 15, 20, 25 and 30 minute time. Plating over time of100 ul, blood agar and additional control. FIG. 40M shows patientisolated cultures treated with blue light. FIG. 40N and FIG. 40Oindicate the optical fiber (POF) kills MSSA and MRSA. The POF experimentprovided light delivered by the optical fiber (POF) that is bactericidalat clinically relevant times to clinically relevant bacteria. It isnoted that completed experiments were in the “right” energy delivery inJ/cm² at 405 nm. Finally, wound healing is NOT affected by bluelight—(HINS light 5 mW/cm² for 1 hour no effect on fibroblast function).FIG. 40P shows patient isolated cultures treated with blue light.

Referring to FIG. 41A, FIG. 41B and FIG. 41C show an intraoperativestabilization of a humerus fracture showing the blue light output. FIG.41A is an exemplary graph that shows the spectral output from thefiberoptic cable used in the device. FIG. 41B and FIG. 41C show the bluelight output from the site of humeral biopsy.

According to aspects of the disclosure, the use of blue light may killMRSA, such that the blue light can provide sterilization oforthopedically relevant pathogenic bacteria, among other things. Forexample, blue light, with wavelengths outside of the UV spectrum, canhave antimicrobial properties for both Gram-negative and Gram-positivebacteria (using blue light for photodynamic bone stabilization. It ispossible, by non-limiting example this antimicrobial effect can be dueto bacteria intracellular porphyrins and the production of cytotoxicreactive oxygen molecules, among other things. Referring to FIG. 41A,the box area 530 highlights the wavelengths of light (405-470 nm) inaccordance with aspects of the disclosure. In particular, thewavelengths of light (405-470 nm) show it is possible for antimicrobialeffects against orthopaedic relevant bacteria. Further, one of the bluelight outputs from the optical fiber at 405 nm (see FIG. 41A, peak ofline 532 in oval 534), show that this wavelength can eradicatemethicillin-resistant S. aureus (MRSA), S. aureus and P. aeruginosa in atime and dose dependent manner due to the production of cytotoxicreactive oxygen molecules. Further, according to aspects of thedisclosure, it is determined that the full spectrum light output duringthe 400 second implant curing process is capable of bactericidalactivity to orthopedically relevant pathogens.

FIG. 42A and FIG. 42B show patient isolated MRSA suspension culturestreated with blue light from an implant 9×160 mm with curing occurringat 400 seconds. FIG. 42A shows a graph of the number of the patientisolated MRSA culture counts versus time in seconds curing with the bluelight. FIG. 42B shows the percent decrease in colony counts versus timein seconds curing with the blue light. FIG. 42A and FIG. 42B illustratesthat 99.9% of bacteria is killed during the 400 seconds curing of theimplant. Wherein the additional time point at 800 seconds shows 100%inactivation of MRSA.

FIG. 42A shows time dependent inactivation of MRSA (samples taken atevery 400 seconds) seen after plating 100 u 1 onto 100 mm blood agarplates and incubating for 24 hrs at 37° C. at 5.5% CO₂. FIG. 42B shows99.9% of bacteria killed during the 400 seconds curing of the implant.An additional time point at 800 seconds is shown with 100% inactivationof MRSA. It is noted that temperature measurements were never above26.2° C. indicating no bacterial inactivation due to heat.

According to methods of the disclosure, blue light inactivation ofbacteria can be dependent on amount or dose of light as described by theequation:Energy(J/cm2)=Intensity(W/cm2)×time(seconds)

Wherein, it is noted that a dose of 36 J/cm2 is toxic to bacteria butnot harmful to mammalian cells. It is possible to use suspensioncultures to determine the effect of blue light on bacterialinactivation, wherein this method was used to study the effect of bluelight on control bacteria, i.e. MSSA (ATCC 29213) and MRSA (ATCC 43300).Further, according to aspects of the disclosure the bacterial strain wasdiluted in 0.9% NSS until reaching an optical density of approximately0.5 McFarland units (1.5×10⁸ CFU/ml). Initial experiments were completedto determine a correct serial dilution in NSS to obtain about 200colonies per 100 ul inoculum onto 100 mm blood agar plates. After finaldilutions to a concentration that is relevant to cause orthopaedicrelated infections (around 10⁵), 3 ml of bacterial suspension was usedfor the light dosing experiments. A time-depending bacterial killing wasnoted in these control experiments (data not shown). These suspensionculture experiments were repeated in duplicate for patient isolated MRSAand data shown in FIG. 42A and FIG. 42B. FIG. 42B shows that a 99.9%killing of MRSA was obtained in 400 seconds used for curing at energylevels that are not toxic to mammalian cells.

According to aspects of methods and embodiments of the disclosure, MRSAis 99.9% inactivated during the 400 seconds cure for the disclosedimplant. It is noted that the aspects of the disclosure of bactericidalactivity associated with an Orthopaedic Implant that is not due to theintrinsic material properties of the implant. According to aspects ofthe disclosure, it is contemplated that the effectiveness of implant onbacterial pathogens most commonly causing Orthopedically relevantinfections can be a way to minimize or manage surgical site infections.It is possible aspects of the disclosure can be used for decontaminationof wounds, implants, infected bone and environmental and biologicallycontaminated surfaces, among other things.

Light fiber matters, such as plastic fiber optics, are incrediblyefficient in the transmission of light with minimal light loss. However,the opposite is the case with any form of diffusing/diffusion lightfiber. The intensity of the light will decrease over length of the fiberdependent upon the amount of light being diffused (length and or area).

When illuminating a material for an antimicrobial effect, the intensityis affected by distance to the subject (inverse square law) with thepower decreasing with distance.

Hence a process of even diffusion of the light in the cladding over thelength of the fiber will result in stronger intensity at the initiationend of the fiber and an ever decreasing amount as distance is increasedfrom the initiation source. This reduction in optical power andintensity negates it's use in the curing of photodynamic implants as theintensity at the distal end has weakened significantly (or the increasedpower to achieve curing at the distal end of the fiber has beenincreased so significantly that there is an overpowering of the fiber atthe proximal end). To correct this, a variable helix of a cut in thecladding, spiraling down the fiber, with the spiral getting tighter andtighter as the light is bleeding out allows for even light dispersionover the length of the fiber.

In some embodiments, the light dispersion system can be in the form of ahigh efficiency glass coupling system where the light dispersion elementis coupled directly to an external mounted LED, laser, or other highpower light source. In this case the fiber is directly abutting thelight source.

In some embodiments, the power density available to be delivered to atreatment site is such that the light fiber does not require contactwith the media it is killing. For example, the power can be sufficientthat it has the ability to provide light to the circumferential area ofthe fiber (speaks to the efficiency of the system) as the inverse squarelaw deals with the intensity of the light as the distance from the fiberincreases.

In some embodiments, fibers may be introduced into the anatomy as astand-alone device (e.g., through an incision), or they may beintroduced into the body via a trocar with the fiber contained within.In some embodiments, fibers may be introduced within a needle (cannula)delivered via catheter through normal body orifices, or into the orificewithout a catheter (e.g., ear, urinary). In some embodiments, fibers canbe delivered via a channel in a scope.

The light fiber can be constructed by either the removal of cladding toachieve the correct light emission program, or using an optically clearand transmissive material that may have a cladding applied to it toachieve the correct emission profile.

Fibers may be small thin (e.g., 0.5 mm, 1.0 mm, 1.5 mm) which areflexible, permitting easy access to small voids, canals, etc., but thefiber may also be larger dependent upon the anatomical locationspecified. For example, a nasal fiber may be 3 mm, and a fiber forvaginal delivery may be 10 mm.

The light emission fiber may be extruded or cast. In some embodiment, acast fiber optic may provide the means to achieve an optical taper(e.g., wider at the light entry side), tapered to the effectivedimension of the required fiber.

In some embodiments, the transmission of light via fiber needs toclosely approximate the size of the LED to the fiber (e.g., a 1 mm LEDneeds a fiber that closely approximates that dimension), otherwise thereare power losses due to the mismatch in size. In some embodiments, adrawn or tapered fiber permits larger LED sources, or multiple LEDsources, to be integrated into the fiber.

All patents, patent applications, and published references cited hereinare hereby incorporated by reference in their entirety. It will beappreciated that several of the above-disclosed and other features andfunctions, or alternatives thereof, may be desirably combined into manyother different systems or applications.

The invention claimed is:
 1. A method for treating tissue, comprising:delivering a catheter to a tissue; delivering one or more optical fibersthrough the catheter to the tissue; activating a light source engagingthe one or more optical fibers; and delivering light energy from thelight source to the one or more optical fibers to provide anantimicrobial effect to the tissue, the one or more optical fibersdispersing the light energy such that intensity of the light energy isdistributed evenly over a length of the one or more optical fibers inboth longitudinal and circumferential directions.
 2. The method of claim1, wherein the light source comprises a plurality of frequencies of thelight energy.
 3. The method of claim 2, further comprising selecting oneor more of the plurality of frequencies of light energy to activatebased on the antimicrobial effect on specific microbial targets.
 4. Themethod of claim 1, wherein the light energy has illumination wavelengthsfrom about 400 nm to about 475 nm.
 5. The method of claim 1, wherein theone or more optical fibers include a cladding covering an outer surfacethereof, and wherein at least a portion of the cladding of the one ormore optical fibers is removed from an outer surface of the one or moreoptical fibers to achieve the even dispersion of the light energy. 6.The method of claim 5, wherein the at least a portion of the cladding isremoved to form a helical spiral along the length of the one or moreoptical fibers.
 7. The method of claim 1, wherein the one or moreoptical fibers disperses the light energy evenly over an active lengthof the one or more optical fibers.
 8. A method for treating tissue,comprising: delivering a catheter to a tissue; delivering one or moreoptical fibers through the catheter to the tissue; selecting a power fora light source engaging the one or more optical fibers; activating thelight source engaging the one or more optical fibers; and deliveringlight energy from the light source to the one or more optical fibers toprovide an antimicrobial effect to the tissue, the one or more opticalfibers dispersing the light energy such that intensity of the lightenergy is distributed evenly over a length of the one or more opticalfibers with an even power distribution over the length of the one ormore optical fibers based on the selected power.
 9. The method of claim8, wherein the light energy is evenly dispersed over the length of theone or more optical fibers in both longitudinal and circumferentialdirections.
 10. The method of claim 8, wherein the light sourcecomprises a plurality of frequencies of the light energy.
 11. The methodof claim 10, further comprising selecting one or more of the pluralityof frequencies of light energy to activate based on the antimicrobialeffect on specific microbial targets.
 12. The method of claim 8, whereinthe light energy has illumination wavelengths from about 400 nm to about475 nm.
 13. The method of claim 8, wherein the one or more opticalfibers disperses the light energy evenly over an active length of theone or more optical fibers.
 14. A method for treating tissue,comprising: delivering a catheter to a tissue; delivering one or moreoptical fibers through the catheter to the tissue; activating a lightsource engaging the one or more optical fibers; and delivering lightenergy from the light source to the one or more optical fibers toprovide an antimicrobial effect to the tissue, the one or more opticalfibers dispersing the light energy such that power of the light energyis distributed evenly over a length of the one or more optical fibers inboth longitudinal and circumferential directions.